PLK3 protein-protein interactions

ABSTRACT

Methods of identifying specific protein-protein interactions involving Polo-like kinase 3 are described, and proteins that bind to Polo-like kinase 3 are identified. Methods of screening compounds for the ability to inhibit or enhance such protein-protein interactions are described.

RELATED APPLICATIONS

[0001] The present invention claims priority from U.S. ProvisionalApplication No. 60/284,176, filed Apr. 17, 2001.

FIELD OF THE INVENTION

[0002] The present invention is related to the identification ofspecific protein-protein interactions, to methods of screening compoundsfor the ability to inhibit or enhance such interactions, and to methodsof affecting physiologic pathways by the inhibition or enhancement ofsuch interactions.

BACKGROUND OF THE INVENTION

[0003] The identification of specific protein-protein interactionsassists in understanding the function of specific proteins. Studies ofinter-protein reactions define cellular interactions involved in basicbiological processes, including the assembly of macromolecularcomplexes, signal transduction and primary/secondary metabolism, andassist in the identification of novel drug targets and/orbiopharmaceutical agents. Additionally, the identification ofprotein-protein interactions allows the development of screening methodsto identify compounds with pharmacological activity (e.g., the abilityto inhibit or enhance specific protein-protein interactions).

[0004] The yeast two-hybrid assay permits analysis of protein-proteininteractions in an intracellular setting, and can screen for largenumbers of potential protein-protein interactions. Fields et al., Nature340:245 (1989); Gyuris et al., Cell 75:791 (1993). The assay utilizes aprotein of interest (the “bait”) which is fused to the DNA bindingdomain of a transcription factor, and a library of target proteins (the“prey”), each of which is fused to a transcriptional activation domain.When a bait protein interacts with a prey protein, a functionaltranscription factor is reconstituted; the transcription factoractivates a reporter gene controlled by a promoter bearing the cognateDNA binding domain site. Detection of the reporter gene productindicates a bait-prey interaction has occurred.

[0005] Each bait analyzed using a conventional yeast two-hybrid assayrequires retransformation and selection of the prey library. As analternative, Bendixen et al., Nuc. Acid Res. 22:1778 (1994) havedescribed an interaction mating strategy, in which the prey library istransformed into a haploid yeast strain and then mated with a strainexpressing the bait. This strategy permits re-use of the librarycontaining yeast strain for multiple assays. The use ofhigher-throughput yeast two-hybrid systems has facilitated the abilityto map the interactions of collections of related proteins. See, e.g.,Bartel et al. (Nature Genetics, 12:72 (1996).

[0006] A semi-automated version of the yeast two-hybrid assay originallydescribed by Gyuris et al (Cell 1993, 75:791-803) has been developed(Buckholz et al., J. Molec. Microbiol. Biotechnol., 1:135 (1999)). Thissystem was used to study the interactions of a bait protein with variousprey protein libraries. Novel protein-protein interactions wereidentified, leading to methods of screening compounds for novelpharmacologic activities.

SUMMARY OF THE INVENTION

[0007] A first aspect of the present invention is a method of screeninga test compound for the ability to inhibit binding of Polo-like kinase 3to a pre-selected interactor protein. The interactor protein is selectedfrom among proteins listed in Table 1 herein; proteins comprising anamino acid sequence selected from the interactor sequences disclosedherein; and fragments of such proteins, where the fragment comprises aPolo-like kinase 3 binding site. The method includes selecting aninteractor protein and detecting whether the test compound inhibitsbinding of the interactor and Polo-like kinase 3, compared to bindingthat would occur in the absence of the test compound.

[0008] A further aspect of the present invention is a method ofscreening a test compound for the ability to bind Polo-like kinase 3 atthe binding site for a pre-selected interactor protein. The methodincludes contacting the test compound with Polo-like kinase 3 (or with aportion of Polo-like kinase 3 containing the appropriate binding site);and then adding the interactor protein and detecting whether the testcompound inhibits the binding of the two proteins, compared to thatwhich would occur in the absence of the test compound.

[0009] A further aspect of the present invention is a method ofidentifying a compound which interferes with the binding of Polo-likekinase 3 to a pre-selected protein, where the method comprises forming amixture of a labeled first protein and a second protein, where oneprotein is Polo-like kinase 3 (or a binding fragment thereof) and theother protein is a protein that binds to Polo-like kinase 3. The testcompound is added to the mixture, and the quantity of the first proteinwhich is bound to the second protein before and after this adding stepis determined. A decrease in the quantity of the first protein which isbound to the second protein after the adding step indicates that thetest compound interferes with the binding of the two proteins.

[0010] A further aspect of the present invention is a method ofscreening allelic variants of Polo-like kinase 3 for altered proteinbinding. The method comprises comparing the binding of allelic variantsof Polo-like kinase 3 to a pre-selected interactor protein.

[0011] A further aspect of the present invention is a method ofinhibiting a physiologic pathway, where the pathway includes the step ofPolo-like kinase 3 binding to an interactor protein. The methodcomprises inhibiting the binding of Polo-like kinase 3 to the interactorprotein.

DETAILED DESCRIPTION

[0012] Automated Yeast two Hybrid System

[0013] In the version of the yeast two-hybrid system described by Gyuriset al., (Cell 1993, 75:791-803), the bait protein is fused to thecarboxyl-terminus of the bacterial LexA protein containing the LexAoperator-DNA binding domain (DBD). The lexA operator's cognate DNAbinding element is incorporated upstream of both a selectable LEU2reporter gene integrated into the yeast genome, and the lacZ gene on anautonomously replicating plasmid. Prey genes are cloned as either randomsequences or cDNAs fused to the carboxyl-terminus of an acid blobtranscription activation domain (AD), B42. Association of the AD-preyfusion with the DBD-bait reconstitutes a functional transcriptionfactor, resulting in expression of the LEU2 and lacZ reporter genes.See, e.g., U.S. Pat. No. 5,283,173 to Fields et al., U.S. Pat. No.5,580,736 to Brent et al. (All US patents cited herein are intended tobe incorporated by reference herein in their entirety)

[0014] The present inventors utilized an automated format for screeningyeast two-hybrids for protein-protein interactions, which includes aliquid array in which pooled library subsets of yeast, expressing up to1000 different cDNAs, are mated to a yeast strain of the opposite matingtype that express the bait protein. See Buckholz et al., J. Molec.Microbiol. Biotechnol. 1:135 (1999); PCT publication No. WO 99/49294, 30September 1999. Proteins that interact (“interactors”) are detected byassaying for β-galactosidase following prototrophic selection.

[0015] The yeast two hybrid (Y2H) assay is carried out in microtiterplates and is partially automated using liquid handling robots. Arrayedprey libraries consist of approximately 1,000 independent pools of 1,000cDNA clones fused to the BN42 transcriptional activation domain gene.Arrayed libraries are frozen in microtiter plates, and sets of aliquotsare thawed as needed. Thawed prey library yeast are mated in microtiterplates with yeast containing bait genes fused to the LexA DNA bindingdomain. Expression of LEU2 and lacZ are used as reporters for bait-preyinteraction in the resulting diploids; cells harboring interactors areselected in media lacking leucine and then tested for β-galactosidaseactivity.

[0016] DNAs encoding interactors are recovered by PCR and sequenced. Anysuitable method of sequencing the interactors may be used; in some casesonly a portion of the interactor cDNA will be sequenced, as the use ofcomprehensive cDNA databases such as GenBank allows the identificationof an expressed sequence tag (EST) from an analysis of a portion of theEST. See, e.g., published Patent Cooperation Treaty application WO0015833 (Burns and Weiner, PCT Application No. PCT/US99/21092).Interactor DNA sequences are processed using an automated sequenceanalysis program, and compared against several genetic databases toidentify interactors.

[0017] The Bait Protein

[0018] The polo-like kinases (Plks) are a family of conservedserine/threonine kinases found in organisms ranging from yeast tohumans; the Plk3 serine/threonine kinase is a mammalian member of thefamily (Ouyang et al., J. Biol. Chem. 272:28646 (1997)). The Plks play arole in normal cell mitosis (Nigg, Curr. Opin. Cell Biol. 10:776 (1998);Glover et al., Genes Dev.12:777 (1998)). At least three Plks have beenidentified in mammals (Plk1, Plk2 and Plk3). The Plks have beenimplicated in the origination or progression of tumors. Plk3 has beensuggested as a candidate tumor suppressor (Dai et al., Genes ChromosomesCancer 27:332 (2000); Li et al, J. Biol. Chem. 271:19402 (1996)).

[0019] Overexpression of Plk3 in mammalian cells suppressesproliferation and inhibits colony formation, and induces chromatincondensation and apoptosis. Plk3 localizes to the cellular cortex and tothe cell midbody during exit from mitosis, and it has been suggestedthat overexpression or ectopic suppression of Plk3 interferes withcellular proliferation by impeding cytokinesis (Conn et al., CancerResearch 60:6826 (2000)).

[0020] It will be appreciated that the term “Polo-like kinase 3”includes naturally occurring allelic variants of the protein; andincludes shortened proteins or peptides wherein one or more amino acidis removed from either or both ends of the full-length protein, or froman internal region of the protein, yet the resulting molecule retainsactivity similar to the full-length protein. The term “Polo-like kinase3” also includes lengthened proteins or peptides wherein one or moreamino acid is added to either or both ends of the protein molecule, orto an internal location in the protein, yet the resulting moleculeretains activity similar to the full-length protein.

[0021] Polo-like kinase 3 used in the present methods is preferably ofmammalian origin, including of human origin. The screening methods ofthe present invention are useful in identifying compounds withpharmacologic activity of potential use in veterinary and/or humantherapeutics.

[0022] As used herein, “Polo-like kinase 3” further refers to a proteinhaving an amino acid sequence encoded by SEQ ID NO:1 (SEQ ID NO:2, seeGenBank Acc. No. U56998), and to proteins having substantial sequencesimilarity thereto that retain Polo-like kinase 3 function. “Substantialsequence similarity” between proteins means at least approximately 90%sequence similarity between the amino acid residue sequences, preferablyat least approximately 95%, and more preferably at least approximately97% or 98% similarity.

[0023] The phrases “percent identity” or “sequence similarity” refer tothe percentage of sequence similarity found in a comparison of two ormore amino acid or nucleic acid sequences. Percent identity can bedetermined electronically, e.g., by using the MegAlign™ program(DNASTAR, Inc., Madison Wis.). The MegAlign™ program can createalignments between two or more sequences according to different methods,e.g., the clustal method. (See, e.g., Higgins, D. G. and P. M. Sharp(1988) Gene 73: 237-244.) The clustal algorithm groups sequences intoclusters by examining the distances between all pairs. The clusters arealigned pairwise and then in groups. The percentage similarity betweentwo amino acid sequences, e.g., sequence A and sequence B, is calculatedby dividing the length of sequence A, minus the number of gap residuesin sequence A, minus the number of gap residues in sequence B, into thesum of the residue matches between sequence A and sequence B, times onehundred. Gaps of low or of no similarity between the two amino acidsequences are not included in determining percentage similarity. Percentidentity between nucleic acid sequences can also be counted orcalculated by other methods known in the art, e.g., the Jotun Heinmethod. (See, e.g., Hein, J. (1990) Methods Enzymol. 183: 626-645.)

[0024] Also included in the definition of the term Polo-like kinase 3are modifications of this protein, its subunits and peptide fragments.Such modifications include substitutions of naturally occurring aminoacids at specific sites with other molecules, including but not limitedto naturally and non-naturally occurring amino acids. For example,conservative amino acid changes may be made, which although they alterthe primary sequence of the protein or peptide, do not normally alterits function. Conservative amino acid substitutions includesubstitutions within the following groups:

[0025] Glycine, alanine;

[0026] Valine, isoleucine, leucine;

[0027] Aspartic acid, glutamic acid;

[0028] Asparagine, glutamine;

[0029] Serine, threonine;

[0030] Lysine, arginine;

[0031] Phenylalanine, tyrosine

[0032] Discussion of Invention, Terms

[0033] The present research identified multiple non-promiscuous proteinsthat interact with the specific bait protein(s) described herein. Anaspect of the present invention is methods of screening test compoundsfor a specific pharmacologic activity, i.e., methods of screening testcompounds for the ability to enhance or inhibit the specific binding ofPolo-like kinase 3 (or a binding portion of Polo-like kinase 3) to aselected interactor protein.

[0034] As used herein, the term “selected interactor protein” refers toa protein chosen from among the proteins identified herein asnon-promiscuous interactors with Polo-like kinase 3 (or a bindingportion of Polo-like kinase 3). Interactor proteins and nucleotidesequences encoding interactor proteins are listed in Tables 1, 2 and 3.It will be apparent to one skilled in the art that the present screeningmethods may be carried out using proteins that comprise an interactorprotein sequence disclosed herein, or that comprise the fragment of theinteractor protein that contains the Polo-like kinase 3 binding site.Similarly, the methods may be carried out using a fragment of theinteractor protein that contains the Polo-like kinase 3 binding site.Proteins with amino acid sequences that are highly similar to theinteractor sequences provided in Tables 1-3, and that contain afunctional Polo-like kinase 3 binding site, may further be used in thepresent methods.

[0035] As used herein, a binding portion of Polo-like kinase 3 refers toa portion or fragment of that protein which is capable of binding aselected interactor protein, as identified herein. The binding site onPolo-like kinase 3 may be different for different interactor proteins.It will be apparent to those skilled in the art that fragments orportions of the full-length bait protein may possess the same ability tobind an interactor protein as that of the full-length bait protein. Thepresent methods of screening compounds for pharmacologic activity may becarried out using full-length bait protein, or a fragment or portion ofthe bait protein which is capable of binding the selected interactorprotein being used in the screening method. Further, the present methodsmay be carried out using a protein comprising the fragment of baitprotein that binds the selected interactor protein, or comprising thecomplete bait protein amino acid sequence.

[0036] As used herein, a compound that inhibits the interaction(binding) between a bait and interactor protein is one that decreasesthe ability of the two proteins to bind, either by directly competingwith one of the proteins for a binding site on the other protein, or byindirectly inhibiting the binding event. Inhibition need not becomplete, as a decrease or reduction in binding may occur. The decreasein binding or interaction of the two proteins is measured in comparisonto that which would occur in the absence of the test compound. Acompound that competes with an interactor protein and binds to a baitprotein may act as either an agonist or antagonist, i.e., it may eithermimic the physiologic effects of the binding event, or prevent(completely or partially) the physiologic effects of the binding event.Such compounds may be partial agonists, partial antagonists, or mixedagonist/antagonists.

[0037] The decrease or reduction in binding may be evidenced, e.g., by adecrease in the number of bound pairs created, reduced binding affinitybetween bound pairs, and/or reduced interaction time between boundpairs. The decrease or reduction in binding may be measured using anysuitable technique as is known in the art. Such techniques will bereadily apparent to those skilled in the art, e.g., competitive bindingassays.

[0038] As used herein, a compound that enhances the interaction (orbinding) between a bait and interactor protein is one that increases theability of the two proteins to bind. The increase in binding of the twoproteins is measured in comparison to that which would occur in theabsence of the test compound. The increase in binding may be evidenced,e.g., by an increase in the number of bound pairs created, increasedbinding affinity between bound pairs, and/or increased interaction timebetween bound pairs. The increase in or enhancment of binding may bemeasured using any suitable technique as is known in the art. Suchtechniques will be readily apparent to those skilled in the art, e.g.,competitive binding assays. The identified compounds may be partialagonists, partial antagonists, or mixed agonist/antagonists.

[0039] Stated another way, the present methods screen compounds for theability to affect (inhibit or enhance) the in vivo or in vitro outcomeof the binding event, via the compound's effect on the binding event.Where, e.g., the protein-protein binding event is a rate-limiting stepin a physiologic pathway, inhibiting the binding event will likewiseinhibit the outcome of the pathway as a whole.

[0040] The bait protein and an interactor protein, as defined herein,make up a specific binding pair. The term specific binding pair, as usedherein, refers to a pair of molecules which are naturally derived orsynthetically produced. One of the pair of molecules has an area on itssurface (or a cavity) which specifically binds to, and is thereforedefined as complementary with, a particular spatial and polarorganisation of the other molecule, so that the pair have the propertyof binding specifically to each other. Examples of types of specificbinding pairs include antigen-antibody, biotin-avidin, hormone-hormonereceptor, receptor-ligand, enzyme-substrate, lgG-protein A.

[0041] The methods of the present invention may utilize labeledproteins. Various methods of detectably labelling proteins are known inthe art (e.g., radiolabeling, enzyme labelling, etc.), and one skilledin the art will be able to identify a suitable method.

[0042] Therapeutic Methods

[0043] The present research has identified previously unknownprotein-protein interactions. Where such interactions are involved inpathologic pathways, inhibition (or enhancement) of the protein-proteininteraction may provide desirable therapeutic effects. Thus, where aprotein-protein interaction is identified as a target for therapeuticintervention due to its involvement in a pathological pathway, methodsof affecting (enhancing or inhibiting) the protein-protein interactionprovide novel therapeutic strategies. For example, the compoundrapamycin links two proteins into a complex, resulting in animmunomodulatory effect. (Choi et al., Science 1996;273(5272):239). Suchmethods comprise providing to a subject in need of such treatment aneffective amount of a compound capable of affecting (enhancing orinhibiting) the identified protein-protein interaction. The effectiveamount will vary according to the subject and condition being treated,and the active compound. Methods of determining effective doses ofactive compounds (e.g., dose response studies) are well known to thosein the art.

[0044] Vectors

[0045] A vector is a DNA molecule, capable of replication in a hostorganism, into which a gene is inserted to construct a recombinant DNAmolecule. (See, e.g., Watson et al., Biotechniques 21:255 (1996)).

[0046] For the Yeast-2-Hybrid experiments described herein, DNA encodingthe bait protein(s) was first cloned into a vector to create an in-framefusion with the bacterial LexA rep gene. In-frame fusion was verified bysequencing. Portions of the bait genes, or the full-length bait gene,were utilized. Portions or fragments of the bait genes are useful ininvestigating specific protein domain associations.

[0047] Bait Control Assays

[0048] Before screening in the Y2H assay, bait control assays may beconducted. Bait control assays include:

[0049] 1. Sequence of fusion junction, to ensure that the bait constructis fused in frame with the LexA DNA binding domain;

[0050] 2. Autoactivation assay, to measure the ability of the LexA-baitfusion protein to activate transcription of the reporter in the absenceof any interacting proteins; and/or

[0051] 3. Repression assay, to measure the ability of the LexA-baitfusion to enter the nucleus and bind to the LexA operators upstream fromthe assay reporter genes.

[0052] Y2H Prey Libraries

[0053] Libraries of cDNA were transformed into yeast and arrayed intomicrowell plates for use in the Y2H assay. For example, arrayed LibraryL4 combined three cDNA libraries derived from human fetal brain, fetalliver, and testis purchased from Invitrogen Corp., Carlsbad, Calif.Another library suitable for Y2H assay is a macrophage libraryconstructed in a modified pYESTrp2 vector. Other cDNA libraries may bescreened using the Y2H methods described herein, as would be apparent toone skilled in the art.

EXAMPLES Example 1 Materials and Methods

[0054] The semi-automated yeast two-hybrid assay method described byBuckholz et al. (J. Molec. Microbiol. Biotechnol. 1:135 (1999)) was usedto investigate protein-protein interactions using Polo-like kinase 3(SEQ ID NO:1) as the bait.

[0055] Bait protein was cloned into the pMW101 vector, and various cDNAlibraries were assayed. Interactor sequences were identified by assayingfor β-galactosidase following prototrophic selection. Insert DNA wasrecovered from the interactors; these DNAs were sequenced and trimmed toremove vector and poor quality regions.

Example 2 Database and Sequence Analysis

[0056] The interactor sequences identified in Example 1 were comparedagainst the current version of separate genetic databases using BLASTN(nucleotide level) and BLASTX (amino acid level). The genetic databasesincluded four publicly available databases: GenBank; Unigene Unique;Unigene gene; and nrpep (each accessible via the internet website forthe National Center for Biotechnology Information (NCBI).

[0057] Interactor sequences were provided identifying nomenclature. Forsome interactors, DNA was recovered and sequenced more than once toensure accuracy. For these interactors, multiple nearly identicalentries occur in the results; the interactor sequence nomenclature willdiffer only in the repetition designation. That is, the project numberwill be preceded by a letter to indicate a repetition, e.g., entriesb111.a22.03.04.c05.p6.6 and b111.b22.03.04.c05.p6.6 indicate tworepetitions, “a” and “b”. These entries do not represent separatediscoveries of the same interactor. Separate discoveries of someinteractors may be present in the results database, but have identifiersdiffering by more than just the sequence repetition designation.

[0058] BLAST Analysis

[0059] Tracefiles were read using Phred to produce files containing theactual basecalls and information about the quality of the reads. Phredis a base-calling algorithm that examines automated sequencer traceswith high sensitivity and probability. See Ewing et al. (1998) GenomeRes. 8:175-185; Ewing and Green (1998) Genome Res. 8:186-194. DNAsequence matching vector sequences were crossed out (X), and sequencematching known mammalian repeats and low complexity DNA sequences weremasked out (N).

[0060] The resulting Y2H interactor sequences were then assembled into“contigs” and “singletons” in a database using Phrap (phragment assemblyprogram; a sequence assembly algorithm developed at the University ofWashington). Where possible, interactor sequences were assembled byPhrap into “contigs” (overlapping contiguous DNA sequences) containingmultiple interactor sequences. Contigs are consensus groupings of atleast partially overlapping sequences. This process provides a number ofcontigs from the Y2H interactor sequences, provides sequence extension,and indicates that the interactor sequence was found elsewhere in theY2H database. That is, the interactor was encountered before in Y2Hanalysis, either with the same bait or another bait. Contig informationindicates either multiple, independent detections of the bait'sassociation with the same interactor, or that the bait shares a commoninteractor with another bait. Contigs including other sequencesidentified with the same bait indicate that the same interactor proteinwas identified multiple times as interacting with the bait. Contigsincluding sequences identified using other baits may suggest linksbetween the function of the bait and the other baits, or may suggestthat the interaction with the bait was non-specific.

[0061] In contrast to contigs, a “singlet” is a sequence containing asingle interactor sequence. That is, this sequence represents aninteractor found only once with the bait, and was not found as aninteractor for other baits.

[0062] Sequences that match known promiscuous interacting proteins wereremoved from the results. “Promiscuous proteins” are those that havebeen found to interact with numerous unrelated baits. The BLAST resultswere searched for the following textual terms, which potentiallyindicate promiscuous proteins: actin; chaperone; collagen related;cytochrome oxidase; ferritin; heat shock; lamin; mitochondri*; PCNA;prote[oa]som*; ribosom*; rRNA; tRNA; ubiquitin; vimentin; zinc fingerprotein. In addition, interactor sequences that have been found withmore than ten unrelated baits are defined as promiscuous interactors andare removed.

[0063] Sequences that align with the complementary, non-coding strand ofa sequence in one of the target databases are also not reported in thepresent results.

[0064] BLAST Results

[0065] The Y2H sequence assemblies (both contigs and singlets) werecompared using BLAST with one or more of the following target databases:UniGene unique, UniGene gene (known genes from the UniGene set),GenBank, nrpep (non-redundant peptide, compared on amino acid level),ESTs from GenBank. These databases contain previously identified andannotated sequences. BLAST stands for Basic Local Alignment Search Tool(see, e.g., Altschul et. al., J. Mol. Evol. 36:290 (1993); Altschul etal., J. Mol. Biol. 215:403 (1990)). Final results included matches withthe best BLAST scores, quality values, assemblies and blast output.

[0066] BLAST results are shown in Tables 1 and 3. A blank BLAST resultscell (no entry in the cell) indicates that the identified interactor didnot have any significant sequence similarity to any entry in thesequence databases queried.

[0067] Nucleotide sequences encoding the bait and interactors areprovided in Table 2.

[0068] Additional information on interactors is provided in Table 3.TABLE 1 BLAST hits of Interactors Cluster_ID Sequence I.D. vs. Unigeneuniq vs. Unigene gene vs. gcgnuc vs. gcgprot Contig4097 seq 3 X13293X13293 E02254 1 Human mRNA for Human mRNA for B- human ‘B myb’MYB-RELATED B-myb gene myb gene oncogene. PROTEIN B (B-MYB). 0 0 0 1E-94Contig4098 seq 4 U01038 X73458 X73458 PLK1_HUMAN Human pLK H. sapiensplk-1 H. sapiens plk-1 SERINE/THREONINE- mRNA, complete mRNA mRNA.PROTEIN KINASE PLK cds 0 0 (EC 2.7.1.-)(PLK-1) 0 (SERINE-THREONINEPROTEIN KINASE 13) (STPK13). 0 Contig4099 seq 5 X75315 X75314 X75314X75314 H. sapiens seb4B H. sapiens seb4D H. sapiens seb4D H. sapiensseb4D mRNA. mRNA mRNA mRNA. 0 0 0 0 Contig4100 seq 6 AF086904 AF086904AF086904 Q9UGF0 Homo sapiens Homo sapiens protein Homo sapiens proteinBA444G7.1 (PROTEIN protein kinase Chk2 kinase Chk2 (CHK2) kinase Chk2(CHK2) KINASE CHK2) (CHK2) mRNA, mRNA, complete cds mRNA, complete cds.(FRAGMENT). complete cds 0 0 1E-36 0 Contig4101 seq 7 no hits no hits nohits no hits Contig4103 seq 8 S57501 J04759 J04759 PP12_RABIT proteinphosphatase Human protein Human protein SERINE/THREONINE type 1catalytic phosphatase I alpha phosphatase I alpha PROTEIN subunit[human, subunit (PPPIA) subunit (PPPIA) PHOSPHATASE PP1- mRNA, 1400 nt]mRNA, 3′ end mRNA, 3′ end. ALPHA 2 CATALYTIC 0 0 0 SUBUNIT (EC 3.1.3.16)(PP-1A). 1E-117 Contig4104 seq 9 AI869704 no hits no hits no hitsw198g02.x1 Homo sapiens cDNA, 3′ end 0 Contig4105 seq 10 AL117237AL117237 AK000726 Q9UJI9 Novel human gene Novel human gene Homo sapiensCdna HYPOTHETICAL 105.9 mapping to mapping to FLJ20719 fis, clone KDAPROTEIN. chomosome 1 chomosome 1 HEP17004. 1E-108 0 0 0 Contig4707 seq11 AC002544 AC002544 AK000739 no hits Homo sapiens Homo sapiens Homosapiens cDNA Chromosome 16 Chromosome 16 BAC FLJ20732 fis, clone BACclone clone CIT987SK-A- HEP08682. CIT987SK-A- 761H5 0 761H5 0 0Contig5000 seq 12 no hits no hits no hits DSR2_HUMAN DOWN SYNDROMECRITICAL REGION PROTEIN 2 (LEUCINE RICH PROTEIN C21- LRP). 1E-89Singlet6481 seq 13 AL117589 AL117589 AB033062 no hits Homo sapiens Homosapiens mRNA; Homo sapiens mRNA for mRNA; cDNA cDNA KIAA1236 protein,DKFZp434N178 DKFZp434N178 partial cds. (from clone (from clone 1E-97DKEZp434N178) DKFZp434N178) 6E-99 5E-99 Singlet6482 seq 14 AJ132583AJ132583 AJ132583 no hits Homo sapiens Homo sapiens mRNA Homo sapiensmRNA for mRNA for for puromycin puromycin sensitive puromycin sensitivesensitive aminopeptidase, partial. aminopeptidase, aminopeptidase, 0partial partial 0 0 Singlet6484 seq 15 D42044 D42044 D42044 Q14700 HumanmRNA for Human mRNA for Human mRNA for KIAA0090 PROTEIN KIAA0090 gene,KIAA0090 gene, KIAA0090 gene, partial (FRAGMENT). partial cds partialcds cds. 9E-73 0 0 0 Singlet6487 seq 16 AF034799 AF034799 AF034799O75334 Homo sapiens liprin- Homo sapiens liprin- Homo sapiens liprin-LIPRIN-ALPHA2. alpha2 mRNA, alpha2 mRNA, alpha2 mRNA, complete 2E-59complete cds complete cds cds. 0 0 0 Singlet6488 seq 17 AB028998AB028998 AB028998 Q9UPS7 Homo sapiens Homo sapiens mRNA Homo sapiensmRNA for KIAA1075 PROTEIN mRNA for for KIAA1075 KIAA1075 protein,(FRAGMENT). KIAA1075 protein, protein, partial cds partial cds. 4E-69partial cds 0 0 0 Singlet6489 seq 18 X66276 X73114 X73114 MYPS_HUMAN H.sapiens mRNA for H. sapiens mRNA for H. sapiens mRNA for MYOSIN-BINDINGskeletal muscle C- slow MyBP-C slow MyBP-C. PROTEIN C, SLOW- protein 0 0TYPE (SLOW MYBP-C) 0 (C-PROTEIN, SKELETAL MUSCLE SLOW-ISOFORM). 2E-83Singlet6491 seq 19 no hits no hits no hits no hits Singlet6492 seq 20 nohits no hits no hits no hits Singlet6497 seq 21 no hits no hits G19371no hits human STS SHGC- 17415. 1E-86 Singlet6498 seq 22 AL079279AL079279 AL079279 no hits Homo sapiens Homo sapiens mRNA Homo sapiensmRNA mRNA full length full length insert full length insert cDNA insertcDNA clone cDNA clone clone EUROIMAGE EUROIMAGE EUROIMAGE 248114. 248114248114 0 0 0 Contig4563 seq 23 X59618 X59618 X59618 1 H. sapiens RR2 H.sapiens RR2 mRNA H. sapiens RR2 mRNA RIBONUCLEOSIDE- mRNA for small forsmall subunit for small subunit DIPHOSPHATE subunit ribonucleotideribonucleotide reductase. REDUCTASE M2 ribonucleotide reductase 0 CHAIN(EC 1.17.4.1) reductase 0 (RIBONUCLEOTIDE 0 REDUCTASE). 0 Contig5071 seq24 no hits no hits no hits RS2_HUMAN 40S RIBOSOMAL PROTEIN S2 (S4)(LLREP3 PROTEIN). 0 Contig5085 seq 25 no hits no hits no hits ENOA_HUMANALPHA ENOLASE (EC 4.2.1.11) (2-PHOSPHO-D GLYCERATE HYDRO- LYASE) (NON-NEURAL ENOLASE) (NNE) (PHOSPHOPYRUVATE HYDRATASE). 0 Contig5087 seq 26no hits no hits no hits CIB_HUMAN SNK INTERACTING PROTEIN 2-28 (SIP2-28)(CALCIUM AND INTEGRIN-BINDING PROTEIN CIB)(KIP). 1E-88 Contig5185 seq 27gnl|UG|Hs#S5565 gnl|UG|Hs#S5565 X93334 NU4M_HUMAN gnl|UG|Hs#S5565gnl|UG|Hs#S5565 X93334 Homo sapiens NADH-UBIQUINONE Human mRNA for HumanmRNA for U1 mitochondrial DNA, OXIDOREDUCTASE U1 small nuclear smallnuclear RNP- complete genome. CHAIN 4 (EC 1.6.5.3). RNP-specific C . . .specific C . . . 0 0 0 0 Singlet6483 seq 28 D21064 D21064 D21064 1 HumanmRNA for Human mRNA for Human mRNA for MITOCHONDRIAL KIAA0123 gene,KIAA0123 gene, KIAA0123 gene, partial PROCESSING partial cds partial cdscds. PEPTIDASE ALPHA 0 0 0 SUBUNIT PRECURSOR (EC 3.4.24.64)(ALPHA-MPP)(P-55)(HA1523) (KIAA0123). 1E-48 Singlet6499 seq 29 M69039 L04636I76429 MA32_HUMAN Human pre-mRNA Homo sapiens pre- Sequence 1 fromCOMPLEMENT splicing factor mRNA splicing factor U.S. Pat. No. 5691447.COMPONENT 1, Q SF2p32, complete 2 p32 subunit 0 SUBCOMPONENT sequence(SF2p32) mRNA, BINDING PROTEIN, 0 complete cds MITOCHONDRIAL 0 PRECURSOR(GLYCOPROTEIN GC1QBP)(GC1Q-R PROTEIN) (HYALURONAN- BINDING PROTEIN 1)(PRE-MRNA SPLICING FACTOR SF2, P32 SUBUNIT)(P33) 7E-36

[0069] TABLE 2 Sequences Sequence No. SEQ ID NO1: ccgcctccga gtgccttgcgcggacctgag ctggagatgc tggccgggct accgacgtca gaccccgggc gcctcatcacPolo-like ggacccgcgc agcggccgca cctacctcaa aggccgcttg ttgggcaaggggggcttcgc ccgctgctac gaggccactg kinase 3 acacagagac tggcagcgcctacgctgtca aagtcatccc gcagagccgc gtcgccaagc cgcatcagcg cgagaagatc (Bait)ctaaatgaga ttgagctgca ccgagacctg cagcaccgcc acatcgtgcg tttttcgcaccactttgagg acgctgacaa catctacatt ttcttggagc tctgcagccg aaagtccctggcccacatct ggaaggcccg gcacaccctg ttggagccag aagtgcgcta ctacctgcggcagatccttt ctggcctcaa gtacttgcac cagcgcggca tcttgcaccg ggacctcaagttgggaaatt ttttcatcac tgagaacatg gaactgaagg tgggggattt tgggctggcagcccggttgg agcctccgga gcagaggaag aagaccatct gtggcacccc caactatgtggctccagaag tgctgctgag acagggccac ggccctgaag cggatgtatg gtcactgggctgtgtcatgt acacgctgct ctgcgggagc cctccctttg agacggctga cctgaaggagacgtaccgct gcatcaagca ggttcactac acgctgcctg ccagcctctc actgcctgcccggcagctcc tggccgccat ccttcgggcc tcaccccgag accgcccctc tattgaccagatcctgcgcc atgacttctt taccaagggc tacacccccg atcgactccc tatcagcagctgcgtgacag tcccagacct gacacccccc aacccagcta ggagtctgtt tgccaaagttaccaagagcc tctttggcag aaagaagaag agtaagaatc atgcccagga gagggatgaggtctccggtt tggtgagcgg cctcatgcgc acatccgttg gccatcagga tgccaggccagaggctccag cagcttctgg cccagcccct gtcagcctgg tagagacagc acctgaagacagctcacccc gtgggacact ggcaagcagt ggagatggat ttgaagaagg tctgactgtggccacagtag tggagtcagc cctttgtgct ctgagaaatt gtatagcttt catgcccccagcggaacaga acccggcccc cctggcccag ccagagcctc tggtgtgggt cagcaagtgggttgactact ccaataagtt cggctttggg tatcaactgt ccagccgccg tgtggctgtgctcttcaacg atggcacaca tatggccctg tcggccaaca gaaagactgt gcactacaatcccaccagca caaagcactt ctccttctcc gtgggtgctg tgccccgggc cctgcagcctcagctgggta tcctgcggta cttcgcctcc tacatggagc agcacctcat gaagggtggagatctgccca gtgtggaaga ggtagaggta cctgctccgc ccttgctgct gcagtgggtcaagacggact aggctctcct catgctgttt agtgatggca ctgtccaggt gaacttctacggggaccaca ccaagctgat tctcagtggc tgggagcccc tccttgtgac ttttgtggcccgaaatcgta gtgcttgtac ttacctcgct tcccaccttc ggcagctggg ctgctctccagacctgcggc agcgactccg ctatgctctg cgcctgctcc gggaccgcag cccagcttaggacccaagcc ctgaaggcct gaggcctgtg cctgtcaggc tctggccctt gcctttgtggccttccccct tcctttggtg cctcactggg ggctttgggc cgaatccccc agggaatcagggaccagctt tactggagtt gggggcggct tgtcttcgct ggctcctacc ccatctccaagataagcctg agccttagct cccagctagg gggcgttatt tatggaccac ttttatttattgtcagacac ttatttattg ggatgtgagc cccagggggc ctcctcctag gataataaacaattttgca SEQ ID NO:3 ATTGGAGCTGGAGAGCCCCTCGCTGACATCCACCCCAGTGTGCAGCCAGAAGGTGGTGGGCGACCACACCACTGCACCGGGACAAGACACCCCTGCACCAGAAACATGCTGCGTTTGTAACCCCAGATCAGAAGTACTCCATGGACAACACTCCCCACACGCCAACCCCGTTCAAGAACGCCCTGGAGAAGTACGGACCCCTGAAGCCCCTGCCACAGACCCCGCACCTGGAGGAGGACTTGAAGGAGGTGCTGCGTTCTGAGGCTGGCATCGAACTCATCATCGAGGACGACATCAGGCCCGAGAAGCAGAAGAGGAAGCCTGGGCTGCGGCGGAGCCCCATCAAGAAAGTCCGGAAGTCTCTGGCTCTTGACATTGTGGATGAGGATATGAAGCTGATGATGTCCACATCTCCCCTCCACTCCCCTGCTTAATAAACTCTAAAAATCCNGNNGNGAAAAAGGNAANNNNNGAANNNCAGNCNAAGGGAGCAAGGAAAAGAAAAANNNGCCGCGGGGGGTGTTTTCCTTTTTTTGCACGGGTAGGGGGTCATCCCCCAAAATGAGGTTGGGTTGGAAAAAAAAATCCTGCTTAAAACCACAAGAAACTTGTTTCACTTATTAGGAAGGAAAAGATTAATTAAAATGGCCG SEQ ID NO:4 GAGGTTCGAGAGACAGGTGAGGTGGTCGACTGCCACCTCAGTGACATGCTGCAGCAGCGGCACAGTGTCAATGCCTCCAAGCCCTCGGAGCGTGGGCTGGTCAGGCAAGAGGAGGCTGAGGATCCTGCCTGCATCCCCATCTTCTGGGTCAGCAAGTGGGTGGACTATTCGGACAAGTACGGCCTTGGGTATCAGCTCTGTGATAACAGCGTGGGGGTGCTCTTCAATGACTCAACACGCCTCATCCTCTACAATGATGGTGACAGCCTGCAGTACATAGAGCGTGACGGCACTGAGTCCTACCTCACCGTGAGTTCCCATCCCAACTCCTTGATGAAGAAGATCACCCTCCTTAAATATTTCCGCAATTACATGAGCGAGCACTTGCTGAAGGCAGGTGCCAACATCACGCCGCGCGAAGGTGATGAGCTCGCCCGGCTGCCCTACCTACGGACCTGGTTCCGCACCCGCAGCGCCATCATCCTGCACCTCAGCAACGGCAGCGTGCAGATCAACTTCTTCCATGATCACACCAAGCTCATCTTGTGCCCACTGATGGCAGCCGTGACCTACATCGACGAGAAGCGGGACTTNCCGCACATACCGNCTGAGTCTNCTGGAGGA GTACGGCTGCTGA SEQ IDNO:5Ttatgctccagcttgtaccgagcttagacatactagtcacggctgcgcagtgtggtgggaattcgaatgcttgggggcg*tg*gaatgtggtagaagaagcagactgaatttactgacagacaggttagcattaaaagattcacaggatatacgctgcaacttcagCGcTacgACTGgaaAGGGGCCTTTGGCCGGCGGCCCCTGTTACCGGCGGCCCCTGTGCGCCTGGGAGCTCCTCCGGGCTTGAGGAAGCCGCCCACGTGCCCTGATGGAGAAAATGGGACTCCAACAGGAGGCcgtgTCCTCACACCTCAGaCTGCGCTCACAGCTcgngaGGATCAAGTTACAATAAACAGtccATTAaCttCtTGcttTCAGGTTTCCCTGgagtcaggcatctctgcacagtccaggcagcccagggctgcagagggctgtacacccgccacatcacagtgggacacagctgag*actgagtggaagcagaaagtcagaagctcatgg*cagactgatgcctatagtagatcatccatgcgcgcagtctaagcgctatgttactt SEQ ID NO:6CTCTCACTCCAGCTCTGGGACACTGAGCTCCTTAGAGACAGTGTCCACTCAGGAACTCTATTCTATTCCTGAGGACCAAGAACCTGAGGACCAAGAACCTGAGGAGCCTACCCCTGCCCCCTgggCTCGATTATGGGCCCTTCAGGATGGATTTGCCAATCTTGAATGTGTGaATGACAACTACCggtTtgggagGgacaaaagctgtgaatATTgctttgaTGaaCcactgctgaaaagaacagataaataccgaacatacagcaagaaacactttcggattttcagggaagtgggtc**taAAAaCttttacattggataccttagaaaatacagtggcaatggaaacctttgtaattccagaacttgtagggaaaggaaaacccccctcttttgaataaccattctt*aaattgcccttgtacttaa*ccggaaataaagg*tttt*ggcttttttgaaccgaccgggaaaaaacaaaccagtttatctctagggctttaaggaatgaatccttttgtcaaaaaccttttgaatgggcccctttgaaaggaaaSEQ ID NO:7AaTTGACGACTGCTGCTGGCACATGGAGCCCCTCTCGCCAATTCCCATTGACCACTGGAACCTGGAGCGGACCGGCCCCCTGAGCACCAGCAGCCCCAGCCGCAGGATGAACGAGGCCGCCGACAGCCGTGACTGTCGCTCCCCGGGACTCCTGGACACCACCCCCATCCGAGGAAGCTGCACTACCCAGAGGAAATTGCAAGAGAAGTCCTCGGGCGCGGGCTCCCTGGGGAATAGCAGGCCGAGCTTTCTGAATTCGGCTCTGTGGGACGTTTGGGACGGGGAAGAGCAGAGGCCTCCAGAGACCCCTCCTCCGGCCCAGATGCCAAGCGCTGGTGGAGCTCAGAAGCCCGAAGGGTTAGAGACACCCAAAGGTGCTAATCGGAAGAAGAACTtGCCCCGAAT SEQ ID NO:8CTCTTTCTGGGGGACTATGTggacAGGGGCAAGCAGTCCTTGGAGACCATctggctgCTGCtggCCTATAAGATCAAGTACCCCGAGAACTTCTTCcTGCTCCGTGGGAACCACGAGTGTGCCAGCATCAACCGCATCTATGGTTTCTACGATGAGTGCAAGAGACGCTACAACATCAAACTGTGGAAAACCTTCACTGACTGCTTCAACTGCCTGCCCATCGCGGCCATAGTGGACGAAAAGATCTTCTGCTGCCACGGAGGCCTGTCCCCGGACCTGCAGTCTATGGAGCAGATTCGGCGGATCATGCGGCCCACAGATGTGCCTGAGGAgggcCTGCTGTGTGACCTGCTGtgGTCTGACCCTGACAAGGACGTGCAggGCtgtggcGAGaaCGaccgtGGCGTCTCtTTTACCTtTGGAGccgaggtggtggccaagtTcctccacaaGCAcgacttggacctcatctgccgAGCACAccag*gtggtagaAGAcggctacGAGTtCtttgccaaGcggcag*ctggtgacaCTTTtCtcagc*tcccaaCTA*Ctgtggcaaggttgacaaatgc*tgcggccatgatg*agtgtgg*acgaga*ccctcatgtgctcttttcagatcctcaagccc SEQ ID NO:9CCTGGCTCCTACTCCAGGTCCCCCGCGGGGTCCCAGCAGCAATTC*GGCTACTCCCCAGGGCAGCAGCA*GACCCACCCCCAGGGTTCTCCAAGGACATCTACACCATTTGGATCAGGGCGTGGTAGAGAAAAAAGAATGTCTAATGAGTTGGAAAATTATTTCAAGCCTTCAATGCTTGAAGATCCTTGGGCTGGCCTAGAACCAGTATATGTAGTGGATATAAGCCAACAATACAGCAATACTCAAACATTCACAGGCAAAAAAGGAAGATACTTTTGTTAACATTTCTGAAATTCAACTGGAAGCTTCATGTGTCAGGAACATCTTGGACAAAACTTTAAGTTGTGTTGATATAAATTTACCCAAAGATGATGACTTTGATTGGATAATTA*GTAaGGTCTTTTTgttaTTTTTCA*TcgtaTCAggTA*ttgtTGATATTA*GAGaAAAAAGTAggatAACtt*G*caaCATTTAGctCT*GGAAGTAcCTACC*ACaatttagagatttaccgtttc*catatatttaacattnctgg*tacantatgggacattgnnctttaatgttttttcaatgttttaaaaataaacatt SEQ ID NO:10AGAGAGAGAGAGAGAGGAGAAAGTGAGCTCAGCGAGTTGGCCGGGTGACACACTGATGAGGGGGTCAAAGGACACTCTGAGTTAGTGCCCTCGGCACACACAGCGAACAGTGATCATGAAAAGAGTGGGCTCAATAATTTTCCATAAACTTGCTCAAGATTCCATGCAGTTGCCATACAGTCTTTGAGGTATGGTCAACCTATAGTAAGTTAGTAAATGTTAAGGGGAGGAAGAAATGGAAACCTAAACATCTACTGCAATGAAAACCAACAGCCATGTCAGTAGGAGTAATTCAACCTTCGTTGAACACATGAAATTGAACACACTCTTGTTTTCCCTGGACCTGGCATCTCCAGGTGTCAACACAGAATTAAGCATCCATAATTGCTCAAAGTTACCTGGCGCATGATGGGTCTTGGTCTTCTTACACTTCTTGGTACTTTTCAATTTCATCCATGTCAACAGCCAAGCCAACACACTGTTGCTCCAATATGTAAAAGGCACTTCTGTAGGGCTGGCATGAGTCAGTCAGTTCAAGACAACCTGAAGGAGTTGAATAACATCTATCCAGTGAGTTCTGCAAGACTTGANGCTCTTTCTCATCCAGCAGCTCTCTGCTGAGCCTGAAN AAGTTGAGAAAAAGAAAASEQ ID NO:11 NTTTTTTNNNNNAGGCCTCCTAGCTCTGATGATGCGCGATGATCAGTCGCTTCTCACGAGATTCGGAACGAGGCGGAGAAGTTGGAGCAAGGCTGGCCGAGAACAGATGAACGGGAGCCCGACTACATGCTAGGGCCACCTAGCGGCGTTACTTCCGAGACCACATGGACGGCTACCGCAAAAATTAGACCTTACATGTGCCGCGGTGGCTACCGCCAGCAGCCGCCTCAGACCGGCCTACTGAGCTCTCCCACCTCTGCATCCCGCCTGGGCCATCCAACCTTGAAGTCCTAAACCACACCTCAGTCACTAAAGGTCTGTTTAAAGTTAAAAAAAAAAAAAAAAAAAAAAAAACCCCGGGGGGGTTGGTGCTTTTTCCCCAAGGGTTTGGGCAAACCCCCCAAAAAGGGTGCGGGTTTTTAANNNNNNTNNCCCNCANCCNNNNNATTTTGCTTTTATTCAACCCCTGGGTTGAAAAGAACATAATAAAATACCCGANCCTTCCCCGCAAAGAAACACCTTTTCGGGATTTTTCAGGGGAAGGGGGGGCCCCTAAAAAAACCTCTTTAACATTTGCCTTCCCCTNGAAAAAATCCCCCGGGGGCCCATTTGAAACCCCCTTTTTAAAAACCCACAACCCTTTGTNAGGGAAAAAGGAAAAACCCCCCCCCCCCTTTTGAATAAACAATTTTCTTGAAATATGCCCCCGGCCCCCTAACGCAAGAAAAAAAAGGTTTTTGGCCTTTTTTTGGGACCCCCCCTGGGGAAAAAACCANCCCCTTTTTTCTCCCCAGGCCTTTAAAGAGAAGAAAAACCTTTTTTGTAAAAAACTTTTTGGAAAGGGGCCCCC TGGAGAGAA SEQ IDNO:12 GCGCAAGCCGGCGTGCGGTCCCGCGGCGCTGCAGTTGTGTCCAGCCGGTCACGGGGCGGGTATGGCGGCCACGTTCTTCGGAGAGGTGGTGAAGGCGCCGTGCCGAGCTGGGACTXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXCGCCCGAGGACAGGGAGGTGCGTCTGCAGCTGGCGCGGAAGAGGGAAGTGCGGCTCCTTCGAAGACAAACAAAAACATCTTTGGAAGTTTCTTTGCTAGAAAAATATCCGTGCTCCAAGTTTATAATTGCTATAGGAAATAATGCAGTAGCATTTCTGTCATCATTTGTTATGAATTCAGGAGTCTGGGAGGAAGTTGGTTGTGCTAAACTCTGGAATGAATGGTGTAGAACAACAGACACTACACATCTGTCCTCCACAGAGGCTTTTTGTGTGTTTTATCATCTAAAATCCAATCCCTCGGTTTTTCTCTGTCAGTGCAGTTGCTATGTTGCAGAAGATCAACAGTATCAGTGGCTGGAAAAGGTTTTTGGCTCTTGTCCAAGGAAGAACATGCAGATAACTATTCTCACATGTCGACATGTTACCGATTATAAAACCTCAGAATCCACCGGCAGCCTTCCTTCTNCTTTNC TGAGAGN SEQ ID NO:13GGGTTGTGGGGGATCTGTGTGGGGTTCTCAACGCAGATCCATCCTGGGGTCTCCCGGGCGGGGATGGCTGACCTCGAGTCCCCTCCCTTCCCGAGAACCCGCTCTGTCCCGAGGGCAGCTAACAAGGGCTGAGCCCCAGGTACAGGTTGCCTCTTCCACGGCAGGAATTTTTACCAAAACCACAAGCAAAAAACAAAACAGACCACCACGACCAACAACAAAGATGGGGGGTAGGGTTTTGTAAAGGTTCTGTTAGGTTCATATTTTTATATCATTTTGCCCATAAATGCGGAATTTGCCGTGGGAATTTGAAGACAAATGATCTATGTTTTTATGGTTCTCTAGGGAAGGTGTTCTGAGGGCCGTGCTCTCTCCAGCTGTGGGAGGCCTGCTCCCTCTGGNGGGCACCCTGNGCAGTGTGTGGGGCCTTTGGAGGCGCTCTTGCCAATGCNACGAGTGTGAGCCTGCAGCGTTGNACGTCCCGACGAAGCTATACTTCTGAGATCGGCTAGAGAGACGCTGACCTTGACAATGTTGATACATCTGCTCAGCTTATTGTGATNAGATGCTCATGG TAAAAAAAAAAATAAAAACSEQ ID NO:14 CGGAGTGTNNNNTTTGATXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXGACCGACCCCTTGGCCAAAAAAAAAAAAAAAGCAAAAAACAAAAACCTACCCTGTTCTGGGTTTTTTCCTCCCTTTAGTTCCACCCCCAACCCCCATTCCCTGGTGTCCTTCTTAGAGATGAAGAAATAATACGGAAACATCTTTCATAGCCACATTAAATAAGAGAAACTGATATACATTATTTTTTTCTTTTTAAAGATGACTTATAAGAACCCTGAAATTTATATAGGTGAGACAATAGAAATAAAAAGATCTTCAGCCAGGCCTTTCTGAAGGAGTTATTCTGCTAAAAATGGTCTTAGTTGTCTGAAAAGCCAGCTCTTGAACCTCTTCACAACAGTATCAACACTGGCTTCTCCCGGTTCATTTTATGCGTGCGAGAAGTCAGTGGTAACTGCTGCAGGGCTTAATACATTAGTGGTAACTGGTTTAAAAAACAAAGACTGTAAGCCTGTGTGTGCCACTGTTTGCTTCAACAGTATATCCTACTAATAAGCCTCACTATTTAATCCAATGAGTTTTAAATCTAAATCTCATTCCCTTCTTCTTTCCCTACCTTNTTTTCTTTTGTTCTTAAAAAAATATTTTGTGTATTTACAGAAATTCATTATTGGGTGGCTTAACGGA TTCCAG SEQ ID NO:15CGGGGCTCTTTTNNNNGATGCCTCCTAGCCTGATGATGTGCGAAATCAGTCGCCGGTGACGAACTGGAAACTGACGCGCGAACGAGTCTGACCGTGCGTGGAGCGTTTAAGAGGACACTTGAGCAATGCATAAGCCAGCGCGTAATAGCTTGCTGGACCGGGGCCAGATGATGTAGGTAGTTCAGCAACGCTATCATTTACCGACCTCCATCAGTGCCATGGAGGCCACCATCACCGAACGGGGCATCACCAGCCGACACCTGCTGATTGGACTACCTTCTGGAGCAATTCTTTCCCTTCCTAAGGCTTTGCTGGATCCCCGCCGCCCCGAGATCCCAACAGAACAAAGCAGAGAGGAGAACTTAATCCCGTATTCTCCAGATGTACAGATACACGCAGAGCGATTCATCAACTATAACCAGACAGTTTCTCGAATGCGAGGTATCTACACAGCTCCCTCGGGTCTGGAGTCCACTTGTTTGGTTGTGGCCTATGGTTTGGACATTTACCAAACTCGAGTCTACCCATCCAAGCAGTTTGACGTTCTGAAGGATGACTATGACTACGNTGTAATCAGCAGCGTCCTCTTTGCCTGGTTTTTGCACCATGATCACTAAGAGACTGCACAGGTCAAAGCTCTGGATCGGGCTTGCGATAAAGAACAAGACTGTGCCTAAAGTGGGAGCCAGGGAGTGTGGGTAAATACAAGTCACGTTGAGTTTGTGGATTGTGGAGATTGGGGGGGAAGGCTAACTAAAACTGGGGAAGATGTGACCTCACCAAACTCTT SEQ ID NO:16 TGGACAGATAGTCTGATTACAGAACAACTAAGGTAATAAGAAGACCAAGGAGAGGCCGCATGGGTGTGCGAAGAGATGAGCCAAAGGTGAAATCTCTTGCGGATCACGAGTGGAATAGAACTCAACAGATTGGAGTACTAAGCAGCCACCCTTTTGAAAGTGACACTGAAATGTCTGATATTGATGATGATGACAGAGAAACAATTTTTAGCTCAATGGATCTTCTCTCTCCAAGTGGTCATTCCGATGCCCAGACGCTAGCCATGATGCTTCAGGAACAATTGGATGCCATCAACAAAGAAATCAGGCTAATTCAGGAAGAAAAAGAATCTACAGAGTTGCGTGCTGAAGAAATTGAAAATAGAGTGGCTAGTGTGAGCCTCGAAGGCCTGAATTTGGCAAGGGTCCACCCAGGTACCTCCATTACTGCCTCTGTTACAGCTTCATCGCTGGCCAGTTCATCTTCCCCCAGTGGACACTCAACTCCAAAGCTCACCCCCTCGAAGCCCTGCCAGGGAAATGGATTCGATGGGAGTCATGACACTTGCAAGGGATCTGAGGAAACATCNGAGAAAGGATGCCAANTTTTGGAAGAAGATGGTTCGGAAGACAAAGCAACAATTAAATGTGAAACTTTTCCTCTTCTACCCCTTAAGCCTTAAAAGGGATAAACTTTTCTTTTTCTAACCCAAGAAGCTGAAAGAGTTAATTTTCTTT SEQ ID NO:17 AGTGCGGCCTGGGCACCCGCTGCCTCTGCTCTTGCCTGCCTGTGGGCATCACCATGCCCCGATGCCTGACTACAGCTGCCTGAAGCCACCCAAGGCAGGCGAGGAAGGGCACGAGGGCTGCTCCTACACCATGTGCCCCGAAGGCAGGTATGGGCATCCAGGGTACCCTGCCCTGGTGACATACAGCTATGGAGGAGCAGTTCCCAGTTACTGCCCAGCATATGGCCGTGTGCCTCATAGCTGTGGCTCTCCAGGAGAGGGCAGAGGGTATCCCAGCCCTGGTGCCCACTCCCCACGGGCTGGCTCCATTTNCCCGGGCAGGCCGGCCTATCCACAATCTAGGAAAGCTGAGGCTACGAAGATCCCTTACGGAGGGAGGGAGGGGGACAGGGAACCCCATTGGCCTGGGGCAACCTGGACCTTAAGCAAGGAACCTTTTGGCAATCTGCCAGAAGTCCGCTTGGAGCCCCGGTGTCCCTGGGAAGGGAAGGGGCCCCCCAAATGGGGGAACAAAGAACAAATGTGCTTTGGGGGCTTTCCCCCGAGAAGGCCCCCCAATGCCAGGGGGTTTTCGTTAAAGAAGTGGGGTTTGGGGCCCCTTTCACAGCCCCCTTTGACAAACCAAAAAAGTCCACATCCCCAGGGGGAAAGGGAAAAGACCCCCTGGGAGAAAGGGGAAAACCCCGGGGCCCCCCC SEQ ID NO:18 GTGGAGCGTGAGTGGCGTTACGAGTGTGACGGGTCTGAAGATGATGCCAATGTAAAAGGGTGCATGAATGGGGACGAGATAATTCCTGGGCCATAATCAGCATACCTCCTCACAGTTGAGGGTAAAAAACACATCTTGATCATAGAGGGAGCAACAAAGGCTGATGCTGCAGAATATTCAGTAATGACAACAGGAGGACAATCATCTGCTAAACTTAGTGTTGACTTGAAACCTCTGAAGATTTTGACACCTCTGACTGATCAGACTGTAAATCTTGGAAAAGAAATCTGCCTGAAGTGTGAAATCTCTGAAAACATACCAGGAAAATGGACTAAAAATGGCCTACCTGTTCAGGAGAGTGACCGTCTAAAGGTGGTTCAGAAGGGAAGGATCCACAAGTTAGTGATAGCCAATGCCCTCACTGAAGATGAAGGTGATTATGTATTTGCACCTGATGCCTACAATGTTACTCTGCCTGCCAAAGTTATGGTATTGATTCTTCTAAGATCATNCTGGATTGTCTTGATGCTGACAACACCATGACGGTGATTGCAGGAAACAGCTTCGTCTTGAGATTCCCATTAGCGGAGAACCACTTCCTAAACCATTTGGAAGCCGGGAAGTAAGGTTCTATTGAAAGGCATGGCCCGGTTAAAAACCGAATTTTAACTTGGTTGACCCACTTCTGGCATTGATTATACTGAAGGGTGACTTCTGGTT TTAC SEQ ID NO:19ACATTG AAAGAAATGCCTTGGGGACATATCAATAACAACGTAACACAGAGCTATTCTATTGGTTATGAAGGTAGCTATGATGCCTCTGCTGATCTCTTTGATGATATTGCTAAAGAAATGGACATTGCAACTGAGATTACCAAAAAATCACAGGATATTTTGTTAAAATGGGGAACATCTTTGGCAGAAAGTCACCCTTCAGAGTCTGATTTTTCACTGAGATCACTTTCTGAAGACTTCATCCAGCCTTCACAAAAATTATCCTTGCAAAGCCTATCTGACTCTAGGCATTCAAGAACATGCTCTCCAACACCTCATTTTCAATCAGATTCAGAATATAATTTTGAAAATAGTCAAGACTTTGTCCATGTTCACAGTCAACTTCAATTTCAGGGTTCACCAAACAAGAATTCATGGGATAAACAGAGCTTTAAAAAAACCTGATTTTATCAGATCTTGATGTAACTATTAAAAAATAAGGATTTTCCTTAAAATGACAACCACAAGCCACCCAACTGGCCAAAAATTTAAAACACTTACCGGAAATAAGAGGCAATCCACCACTGGCGGCCTTCAGGATCATTTAAGAGCCAC SEQ ID NO:20AATATACAACATGGCTCGAGC CCATGCCTGCAGGCGCCACGTCTGCACAAGAGAGAGATGACGACATCATATGGACATCCACACTCGCAAAGCAGGTCAGGAGGACTGGCATGCCCCTGTCTCCCCAGCACCCCATTTGTAGCCTTTTCTCAGGTTGAGTAAATAGTTCTGTATTAGGAAAGGCCCTCTTGCCTCCACAACTCCTTCCCCACCTTGGTGACATCATTCATCGTGGTTCTGCCACTTCCTAGGAGCCCATGGAGGAGAGGCA CCAA SEQ ID NO:21AGGGGNNNNNCCCTTTTNTTATCCTCCTACTTGAGGATGTGCGAAATTATGCCTCTGACGAATTGGAACGAGGGGCTAGGCGTAGATTATGGCGGTCTGTCAAATCTACTTGGGGAGCAGCTAATTCTGGACGAGTTAGCCGGCCTGCTGCGAGGCCGCTCATAAAGCTGGGACTCCATGACTTACATCACTTCCACTCCCTTGCCATCCGAGGTGACATGCCCAATCAGATTGTGCAGATCTTGACCCAGGATCATGGCATGGAATTAATATGTTGCTTTGGCAACACCAGTTGGGACAGAAGCCTTCTGCTCTTCAGGGCAAAACAAACCATAGAGACTCATCCAATCCCTGAATCACTGATAGAAAAAGGGAAAGAAAAGAACAGATTAAGATTCCAGAAGCAGTGAGATGGGAGGGCANGAAGACCAAGAAAGATATTGAAAGGTTTTATATTGAGAAATATGTTCATTCTTCTTAATTCCTAACAATCANGCAGCCGCAAAACCTGCAGGAGCTTTTGGTAAAATGTCCAAGGCACAATATTGGAAAGAATCATAATCTGGTCCCCAATGGTTTTGAACCAAACCTTGAAGAAGAAGTGAAATCGTGGGGAGGTGAATGAGACCCTAGGGAAATCTCTGGAAATGGGGAAAAGGGCCCATAGGGAAAAAAGGGGGGCCCCCGGGTTATATGGGGTTTATATGGGAAAAGAGGTCTTTCCTTTTTTTTGGGGGGTATATTTTTTTTTTTAAAGGAGATCCAACCCCCGGGCTCTGGGGCTTTTAAAAAAAAAATTTTGGGGAGGTTCCCCGGGGGCCCTCCTCCTTAAAAAACCCCACCCCCCCGG GGTTTTTTTTCAAGGC SEQID NO:22 AGGN GGCCATATACAGTATCAGTGCTTTCCTGGTTATAAGCTCCATGGAAATTCATCAAGAAGGTGCCTCTCCAATGGCTCCTGGAGCGGCAGCTCACCTTCCTGCCTGCCTTGCAGATGTTCCACACCAGTAATTGAATATGGAACTGTCAATGGGACAGATTATGACTGTGGAAAGGCAGCCCGGATTCAGTGCTTCAAAGGCTTCACGCTCCTAGGACTGTCTGAAATCACCTGTGAAGCCGATGGCCAGTGGAGCTCTGTGTTCCCCCACTGTGAACACACTTCATGTGGTTCTCTTCCAATGATACCAAATGCGGTCATCTCTTCTCGGAAGGGCCTGGCCATCCTGAAACTCTGCAAAGAAATCCAACATGCGCTGGGCCTTTGTAAGTAAACCTGTACCTTGAGTTACTTTTTTTATTAGGGGGAATAAATTGGGAATTCCTTGGAAAAAAATTATTAAATGGTGCATTTTAAAAAATCGCGGGTTTTCCTTTTAAAAATTTTTTAATTGGAGCTGCCTTACCTTAAAAAAAAATGAAATGTGGG SEQ ID NO:23GAAATGGCCCCTTCCCCTTGAACCCTCTGTCATNNGTATAGGTNGNCNTCATGATAATTCAGTCGACATCGGNTCGCCATCTNANGATCTGNGGACATCTGCACGCGCNGAGGATACACAGTGCAGAACACATGTGGCGGGCACGCGTACTGAGATCCGCACACTAGCAGCCAAAAGCTCATTACCGCCCCGCATAGTTGCATAGTCATCTTAGCAGGAGCCGCCATCATGTAACATACATATCGTGAACGCTTACATTCACCGCATTGACACTTACATAAAAGATCCCAAAGAAAGGGAATTTCTCTTCAATGCCATTGAAACGATGCCTTGTGTCAAGAAGAAGGCAGACTGGGCCTTGCGCTGGATTGNGGACAAAGAGGCTACCTATGGTGAACGTGTTGTAGCCTTTGCTGCAGTGGAAGGCATTTTCTTTTCCGGTCTTTTGCGTCGATATTCTGGCTCAAGAAACGAGGACTGATGCCTGCCTCACATTTCTAATGGACTATATAGCGAGAATAGGGTTACACTGGGAATTTGCTTGCCTGAGGTCCAAACACCCGGCCCCAAACCTTCGGNGGGAAAGTAGGAGAATAATTTCATGCTGTCCGTATGAACACGGATCCTAACTGAGGCTTGCCTGTAACGTAATTGGATGATTGCCCTCAATGAGCATACTTTGGTTTTGGCAACAACATTCCTGAACCGGTTTACCAGTTTCAAAAAAAACCTTTGCTTTTGGAATTTCCCTGAGGAACTACTTTTGAAAAGAGG CCGTTAAAA SEQ IDNO:24 AGGGGNTCTTTTNNNNNGATGCCTCCTACCCTGATGATGGTGCGCAGATTAGTCGCNCGTGTGACGAGATCTGGACATATCGCACGGCGCATGGCGCCCAACGCATAGCAGGACGCTCGCAGAAGCAGCATGAGCCCCGGCTCACATTCCCGCGCGAAGAACATGCGTAACCAACAGCGTGTCTGGACCACAGCCCTGTCACCCTGACACTGAATCGCACGCAATGCTAGCTGCCCCTTTCCCGTCCTGGGCACCCCGAGTCTCCCCCGACCCCGGGTCCCAGGTATGCTCCCACCTCCACCTGCCCCACTCACCACCTCTGCTAGTTCCAGACACCTCCACGCCCACCTGGTCCTCTCCCATCGCCCACAAAAGGGGGGGCACGAGGGACGAGCTTAGCTGAGCTGGGAGGAGCAGGGTGAGGGTGGGCGACCCAGGATTCCCCCTCCCCTTCCCAAATAAAGATGAGGGTACTAAAANAAAAAAAAAAAANAAAANNNNCCCCAGAAAGGTTTGGGTTTTTTCCCCAAGGGGTTGGGAAAGATTCCAAAAAAGGGGTGGCGTGGTGTGAAAANNNNNNAAAACCNNNNGNAATNGAACCCTTTGTTATTCAAAAGCTTGTTGGGAAAAGGAAAACCCCCCCCCTTTGAACTAACAATTTTTAAAATTGAACTGTTACTAAACAGAAAAAAAAGTTTTTGGTTTTTTTTGATCTGACTGTAATGAAAANNNNATTTTTTCCTAGGGTTTTAAAGAGTAATACTTTTTGTAAAACTCTTTGGAAGTGGGCCTTTGGAAAGGAAAAAATTGTTTTNTAGGGAAACTATTTAAAG SEQ ID NO:25AAGGACTACCCAGTGGTGTCTATCGAAGATCCCTTTGACCAGGATGACTGGGGAGCTTGGCGAGAAGTTCACAGCCAGTGCAGGAATCCAGGTAGTGGGGGATGATCTCACAGTGACCAACCCAAAGAGGATCGCCAAGGCCGTGAACGAGAAGTCCTGCAACTGCCTCCTGCTCAAAGTCAACCAGATTGGCTCCGTGACCGAGTCTCTTCAGGCGTGCAAGCTGGCCCAGGCCAATGGTTGGGGCGTCATGGTGTCTCATCGTTCGGGGGAGACTGAAGATACCTTCATCGCTGACCTGGTTGTGGGGCTGTGCACTGTGCAGATCAAGACTGGTGCCCCTTGCCGATCTGAGCGCTTGGCCAAGTACAACCAGCTCCTCAGAATTGAAGAGGAGCTGGGCAGCAAGGCTAAGTTTGCCGGCAGGAACTTCAGAAACCCCTTGCCAAGTAAGCTGTGGGCAGGCAAGCCCTTCGGTCACCTGTTGTCTACACAGANCCCTTCCCTCGTGTCAGCTCAGGCAGCTCGAGGCCNNCGACCAACACTTGCAGGGGTCCNTTGCTAGTAGCGCCCCACCCGCGTGGAGTTCGTACCGCTTCTTTAGACTTCNTACAGAAGCCAAGCTTCCTT GGAGCCCTG SEQ IDNO:26 GGATGCCTCCTACCTCTGATGATGTGCCATAATTAGTCACCTGTCACGGATTCGAATCGAGCGCGGACGAGTCGACCATGCTGTGCGCGCGAGGCGACCAGCGGGCGCTCTAACAGCCGCCTGATCGCGGACCTGTTGAGCGCCGACTAAGACTAGACGTTATTGACCACTCACGTGAACCTACTAGCCCACAGGCGGTTTTGTGAGCTGCTTCCCCAGGAGCAGCGGAGCGTGGAGTCGTCACTTCGGGCACAAGTGCCCTTCGAGCAGATTCTCAGCCTTCCAGAGCTCAAGGCCAACCCCTTCAAGGAGCGAATCTGCAGGGTCTTCTCCACATCCCCAGCCAAAGACAGCCTTAGCTTTGAGGACTTCCTGGATCTCCTCAGTGTGTTCAGTGACACAGCCACGCCAGACATCAAGTCCCATTATGCCTTCCGCATCTTTGACTTTGATGATGACGGAACCTTGAACAGAGAAGACCTGAGCCGGCTGGTGAACTGCCTCACGGGAGAGGGCGAGGACACACGGCTTANTGCGTCTGAGATGAAGCAACTCATCGACAACATTCTGGAGGAGTCTGACATTGACAGGATGGACCATCAACTCTCTGAGTNCAGCACGTNATCTCCCGTCTTCAGACTTTGCAAGTTCTTTAGAATGCCTGTGACAGAACCCCAGCTGGGTCTGGACCTTGTCAAAACCTTTACTGTGACTTTGGCAAGTAAACTTGTTGCAATGCGGCCACTTGGCAACTGACTGG SEQ ID NO:27 TGTGGACCTCGTCGATGAACAGCACTCCTTCCTCAACCGGGCCCTGGAGAGTGACATGGCGCCTGTCCTGATCATGGCCACCAACCGTGGCATCACGCGAATCCGGGGCACCAGCTACCAGAGCCCTCACGGCATCCCCATAGACCTGCTGGACCGGCTGCTTATCGTCTCCACCACCCCCTACAGCGAGAAAGACACGAAGCAGATCCTCCGCATCCGGTGCGAGGAAGAAGATGTGGAGATGAGTGAGGACGCCTACACGGTGCTGACCCGCATCGGGCTGGAGACGTCACTGCGCTACGCCATCCAGCTCATCACAGCTGCCAGCTTGGTGTGCCGGAAACGCAAGGGTACAGAAGTGCAGGTGGATGACATCAAGCGGGTCTACTCACTCTTCCTGGACGAGTCCCGCTCCACGCAGTACATGAAGGAGTACCAGGACGCCTTCCTCTTCAACGAACTCAAAGGCGAGACCATGGACACCTCCTGAGTTGGATGTCATCCNCCGACCCCACCCTGTTTTCCACCAGAGTTCTGACACTGTGACTCTGTATAAAATGGGTGGGAAGCTGCACCCACCCTGTGTATGTGTGGTTGCCCTGAGCCCNCNGAATGCCANAAAATAAAA AATAATTCCTTAGAAG SEQID NO:28 AAGACGCAGCTGACATCAATGCTCATGATGAACCTGGAATCCAGGCCTGTGATCTTCGAGGATGTGGGGAGGCAGGTGCTGGCCACTCGCTCCAGAAAGCTGCCGCACGAGCTGTGCACGCTCATCCGCAACGTGAAGCCGGAAGATGTGAAGAGAGTCGCTTCTAAGATGCTCCGAGGGAAGCCGGCAGTGGCCGCCCTGGGTGACCTGACTGACCTGCCCACGTATGAGCACATCCAGACCGCCCTGTCGAGTAAGGACGGGCGCCTGCCCAGGACGTACCGGCTCTTCCGGTAGAACCGCTCCCCGGCCTGACAGACCCAGGGAGCTGCAGCTGGAGCCCGTTCCCGTGCGTGTTAGTTTGTACACGAATTTAGTCTAAAAAGCTGTCTGGTTGTATAAACGGTGCAAACAATGTCGCCACAGCACCCACGCGGATTGCATTCTTTTGGAACTCAATGTGCCGATCAGTGGAGTCAGTATCGAGCCTGACCACCGCAAGCCAGGAAGCANGTGAAGTGCCCAGCGCTGGAGTGCATCGTGCCACGAGGAGGGCGGTCGGTGCTTCCCTTCTCGAGCTGTGGGCACATAGCGCCCCGCAGGTTCCTTGGATGTAGCCCTGATCTAG GTAGCACC SEQ ID NO:29CTCTTTTNTTTATCCTCCTACTTGATGATGTGCGAAATCAGTACCGCTGACGAACTGGGAACTGAGCGGCGGATACTGGAGTGGCATCGACAAGTCGAATCGAGGTCGCACCAAGCGGCGACAGCTGATAACCATCACGAACAGCCTTGCATCATTGAGCACCGCATCACTGCCAACAGTTGTAGGCACGACTAACATCCACTCGCAAGGGCAGAAGGTTGAAGAACAGGAGCCTGAACTGACATCAACTCCCAATTTCGTGGTTGAAGTTATAAAGAATGATGATGGCAAGAAGGCCCTTGTGTTGGACTGTCATTATCCAGAGGATGAGGTTGGACAAGAAGACGAGGCTGAGAGTGACATCTTCTCTATCAGGGAAGTTAGCTTTCAGTCCACTGGCGAGTCTGAATGGAGGATACTAATTATACACTCAACACAGANTCCTTGGACTGGCCCTTATATGACCACCCTATGAATTTCCTTGCCGACCGAGGGGGTGACAACACTTTTGCCAGATAACCGGTGGAACTCAGCCCAAGCCTTGAGCAACAGGGAGTCCATTACTTTTCTTGGAGAACCTTAGGAAATTTTGTCAAGAGAGCCCTTTAAACCCCCACCAATGCCTGAAAAGCCCTTAGTTTTCAATGGGCAGGGCCTTTGGCCCCAGGGGAACAAAAAACCCTCACCCTTTAAAAGCTTTAACAACTGGGCCCTTTTGGAAAAGGGGAGTTTTCAACCCCCCAAAATCCCAAAAGGGGGGGAAAAAAAACCCCCCCAATTTTAAAAAATTTTTTTGGGTTTGGGGGGGGGGCCCCCAATATTAAAATAAAAAAATTTTTTTTTTCTGTTGACACAAAAAA

[0070] TABLE 3 BLAST alignment data for interactors Percent InteractorHit ID Hit Annotation ID Overlap Score P Value UG Cluster Contig4097X13293 Human mRNA for B-myb gene 99 499 981 0 Hs.179718 /cds = (127,2229)/gb = X13293 /gi = 29471/ug = Hs.179718/len = 2627 Contig4098U01038 Human pLK mRNA, complete cds 98 954 1792 0 Hs.77597 /cds = (63,1874)/gb = U01038 /gi = 393016/ug = Hs.77597/len = 2178 Contig4099X75315 H. sapiens seb4B mRNA/cds = (0, 693) 97 281 496 0 Hs.247500 /gb =X75315/gi = 407420 /ug = Hs.247500/len = 1438 Contig4100 AF086904 Homosapiens protein kinase Chk2 95 418 646 0 Hs.146329 (CHK2) mRNA, completecds /cds = (0, 1631)/gb = AF086904 /gi = 3982839/ug = Hs.146329/len =1735 Contig4101 no hit unknown sequence Contig4103 S57501 proteinphosphatase type 1 catalytic 98 635 1180 0 Hs.183994 subunit [human,mRNA, 1400 nt] /cds = (11, 1036)/gb = S57501 /gi = 298963/ug =Hs.183994/len = 1388 Contig4104 H57957 yr12h06.s1 Homo sapiens cDNA, 3′89 305 357 9E-98 Hs.230106 end/clone = IMAGE:205115 /clone_end = 3′/gb =H57957 /gi = 1010789/ug = Hs.230106/len = 390 Contig4105 AL050141 Homosapiens mRNA; cDNA 99 332 642 0 Hs.227834 DKFZp586O031 (from cloneDKFZp586O031)/cds = UNKNOWN /gb = AL050141/gi = 4884352 /ug =Hs.227834/len = 2353 Contig4707 U46025 Human translation initiationfactor eIF- 100 722 1431 0 Hs.4835 3 p110 subunit gene, complete cds/cds = (0, 2741)/gb = U46025 /gi = 1718196/ug = Hs.4835/len = 2742Contig5000 DSR2_HUMAN DOWN SYNDROME CRITICAL 94 168 328 1E-89 noneREGION PROTEIN 2 (LEUCINE RICH PROTEIN C21-LRP). Singlet6481 AL117589Homo sapiens mRNA; cDNA 95 228 361 6E-99 Hs.134970 DKFZp434N178 (fromclone DKFZp434N178)/cds = (0, 808) /gb = AL117589/gi = 5912152 /ug =Hs.134970/len = 1907 Singlet6482 AJ132583 Homo sapiens mRNA forpuromycin 99 364 706 0 Hs.132243 sensitive aminopeptidase, partial /cds= (85, 2712)/gb = AJ132583 /gi = 4210725/ug = Hs.132243/len = 4049Singlet6484 D42044 Human mRNA for KIAA0090 gene, 97 505 805 0 Hs.154797partial cds/cds = (0, 2718)/gb = D42044 /gi = 577300/ug = Hs.154797/len= 5726 Singlet6487 AF034799 Homo sapiens liprin-alpha2 mRNA, 96 642 10720 Hs.30881 complete cds/cds = (169, 3942) /gb = AF034799/gi = 3309532/ug = Hs.30881/len = 4060 Singlet6488 AB028998 Homo sapiens mRNA forKIAA1075 99 345 662 0 Hs.6147 protein, partial cds/cds = (0, 4202) /gb =AB028998/gi = 5689486 /ug = Hs.6147/len = 4692 Singlet6489 X66276 H.sapiens mRNA for skeletal muscle 96 493 821 0 Hs.169849 C-protein/cds =(96, 3512)/gb = X66276 /gi = 36500/ug = Hs.169849/len = 3833 Singlet6491no hit unknown sequence Singlet6492 no hit unknown sequence Singlet6497G19371 human STS SHGC-17415. 96 199 325 1E-86 none Singlet6498 AL079279Homo sapiens mRNA full length insert 97 321 565 0 Hs.8963 cDNA cloneEUROIMAGE 248114 /cds = UNKNOWN/gb = AL079279 /gi = 5102585/ug =Hs.8963/len = 2428 Contig4563 X59618 H. sapiens RR2 mRNA for small 971492 2623 0 Hs.75319 subunit ribonucleotide reductase /cds = (194,1363)/gb = X59618 /gi = 36154/ug = Hs.75319/len = 2475 Contig5071 O55215RIBOSOMAL PROTEIN S2. 99 240 486 0 none Contig5085 ENOA_MOUSE ALPHAENOLASE (EC 4.2.1.11)(2- 94 315 612 0 none PHOSPHO-D-GLYCERATE HYDRO-LYASE)(NON-NEURAL ENOLASE)(NNE). Contig5087 CIB_HUMAN SNK INTERACTINGPROTEIN 2-28 90 184 326 1E-88 none (SIP2-28)(CALCIUM ANDINTEGRIN-BINDING PROTEIN CIB) (KIP). Contig5185 gnl|UG|Hs#S5565gnl|UG|Hs#S5565 Human mRNA for 100 320 634 0 none U1 small nuclearRNP-specific C . . . Singlet6483 Q16704 ENOLASE (EC 4.2.1.11)(2- 99 315637 0 none PHOSPHOGLYCERATE DEHYDRATASE)(2-PHOSPHO-D- GLYCERATEHYDRO-LYASE). Singlet6499 ENOA_HUMAN ALPHA ENOLASE (EC 4.2.1.11)(2- 100315 640 0 none PHOSPHO-D-GLYCERATE HYDRO- LYASE)(NON-NEURALENOLASE)(NNE) (PHOSPHOPYRUVATE HYDRATASE).

[0071]

1 29 1 2169 DNA homo sapiens CDS (37)..(1860) 1 ccgcctccga gtgccttgcgcggacctgag ctggag atg ctg gcc ggg cta ccg 54 Met Leu Ala Gly Leu Pro 1 5acg tca gac ccc ggg cgc ctc atc acg gac ccg cgc agc ggc cgc acc 102 ThrSer Asp Pro Gly Arg Leu Ile Thr Asp Pro Arg Ser Gly Arg Thr 10 15 20 tacctc aaa ggc cgc ttg ttg ggc aag ggg ggc ttc gcc cgc tgc tac 150 Tyr LeuLys Gly Arg Leu Leu Gly Lys Gly Gly Phe Ala Arg Cys Tyr 25 30 35 gag gccact gac aca gag act ggc agc gcc tac gct gtc aaa gtc atc 198 Glu Ala ThrAsp Thr Glu Thr Gly Ser Ala Tyr Ala Val Lys Val Ile 40 45 50 ccg cag agccgc gtc gcc aag ccg cat cag cgc gag aag atc cta aat 246 Pro Gln Ser ArgVal Ala Lys Pro His Gln Arg Glu Lys Ile Leu Asn 55 60 65 70 gag att gagctg cac cga gac ctg cag cac cgc cac atc gtg cgt ttt 294 Glu Ile Glu LeuHis Arg Asp Leu Gln His Arg His Ile Val Arg Phe 75 80 85 tcg cac cac tttgag gac gct gac aac atc tac att ttc ttg gag ctc 342 Ser His His Phe GluAsp Ala Asp Asn Ile Tyr Ile Phe Leu Glu Leu 90 95 100 tgc agc cga aagtcc ctg gcc cac atc tgg aag gcc cgg cac acc ctg 390 Cys Ser Arg Lys SerLeu Ala His Ile Trp Lys Ala Arg His Thr Leu 105 110 115 ttg gag cca gaagtg cgc tac tac ctg cgg cag atc ctt tct ggc ctc 438 Leu Glu Pro Glu ValArg Tyr Tyr Leu Arg Gln Ile Leu Ser Gly Leu 120 125 130 aag tac ttg caccag cgc ggc atc ttg cac cgg gac ctc aag ttg gga 486 Lys Tyr Leu His GlnArg Gly Ile Leu His Arg Asp Leu Lys Leu Gly 135 140 145 150 aat ttt ttcatc act gag aac atg gaa ctg aag gtg ggg gat ttt ggg 534 Asn Phe Phe IleThr Glu Asn Met Glu Leu Lys Val Gly Asp Phe Gly 155 160 165 ctg gca gcccgg ttg gag cct ccg gag cag agg aag aag acc atc tgt 582 Leu Ala Ala ArgLeu Glu Pro Pro Glu Gln Arg Lys Lys Thr Ile Cys 170 175 180 ggc acc cccaac tat gtg gct cca gaa gtg ctg ctg aga cag ggc cac 630 Gly Thr Pro AsnTyr Val Ala Pro Glu Val Leu Leu Arg Gln Gly His 185 190 195 ggc cct gaagcg gat gta tgg tca ctg ggc tgt gtc atg tac acg ctg 678 Gly Pro Glu AlaAsp Val Trp Ser Leu Gly Cys Val Met Tyr Thr Leu 200 205 210 ctc tgc gggagc cct ccc ttt gag acg gct gac ctg aag gag acg tac 726 Leu Cys Gly SerPro Pro Phe Glu Thr Ala Asp Leu Lys Glu Thr Tyr 215 220 225 230 cgc tgcatc aag cag gtt cac tac acg ctg cct gcc agc ctc tca ctg 774 Arg Cys IleLys Gln Val His Tyr Thr Leu Pro Ala Ser Leu Ser Leu 235 240 245 cct gcccgg cag ctc ctg gcc gcc atc ctt cgg gcc tca ccc cga gac 822 Pro Ala ArgGln Leu Leu Ala Ala Ile Leu Arg Ala Ser Pro Arg Asp 250 255 260 cgc ccctct att gac cag atc ctg cgc cat gac ttc ttt acc aag ggc 870 Arg Pro SerIle Asp Gln Ile Leu Arg His Asp Phe Phe Thr Lys Gly 265 270 275 tac accccc gat cga ctc cct atc agc agc tgc gtg aca gtc cca gac 918 Tyr Thr ProAsp Arg Leu Pro Ile Ser Ser Cys Val Thr Val Pro Asp 280 285 290 ctg acaccc ccc aac cca gct agg agt ctg ttt gcc aaa gtt acc aag 966 Leu Thr ProPro Asn Pro Ala Arg Ser Leu Phe Ala Lys Val Thr Lys 295 300 305 310 agcctc ttt ggc aga aag aag aag agt aag aat cat gcc cag gag agg 1014 Ser LeuPhe Gly Arg Lys Lys Lys Ser Lys Asn His Ala Gln Glu Arg 315 320 325 gatgag gtc tcc ggt ttg gtg agc ggc ctc atg cgc aca tcc gtt ggc 1062 Asp GluVal Ser Gly Leu Val Ser Gly Leu Met Arg Thr Ser Val Gly 330 335 340 catcag gat gcc agg cca gag gct cca gca gct tct ggc cca gcc cct 1110 His GlnAsp Ala Arg Pro Glu Ala Pro Ala Ala Ser Gly Pro Ala Pro 345 350 355 gtcagc ctg gta gag aca gca cct gaa gac agc tca ccc cgt ggg aca 1158 Val SerLeu Val Glu Thr Ala Pro Glu Asp Ser Ser Pro Arg Gly Thr 360 365 370 ctggca agc agt gga gat gga ttt gaa gaa ggt ctg act gtg gcc aca 1206 Leu AlaSer Ser Gly Asp Gly Phe Glu Glu Gly Leu Thr Val Ala Thr 375 380 385 390gta gtg gag tca gcc ctt tgt gct ctg aga aat tgt ata gct ttc atg 1254 ValVal Glu Ser Ala Leu Cys Ala Leu Arg Asn Cys Ile Ala Phe Met 395 400 405ccc cca gcg gaa cag aac ccg gcc ccc ctg gcc cag cca gag cct ctg 1302 ProPro Ala Glu Gln Asn Pro Ala Pro Leu Ala Gln Pro Glu Pro Leu 410 415 420gtg tgg gtc agc aag tgg gtt gac tac tcc aat aag ttc ggc ttt ggg 1350 ValTrp Val Ser Lys Trp Val Asp Tyr Ser Asn Lys Phe Gly Phe Gly 425 430 435tat caa ctg tcc agc cgc cgt gtg gct gtg ctc ttc aac gat ggc aca 1398 TyrGln Leu Ser Ser Arg Arg Val Ala Val Leu Phe Asn Asp Gly Thr 440 445 450cat atg gcc ctg tcg gcc aac aga aag act gtg cac tac aat ccc acc 1446 HisMet Ala Leu Ser Ala Asn Arg Lys Thr Val His Tyr Asn Pro Thr 455 460 465470 agc aca aag cac ttc tcc ttc tcc gtg ggt gct gtg ccc cgg gcc ctg 1494Ser Thr Lys His Phe Ser Phe Ser Val Gly Ala Val Pro Arg Ala Leu 475 480485 cag cct cag ctg ggt atc ctg cgg tac ttc gcc tcc tac atg gag cag 1542Gln Pro Gln Leu Gly Ile Leu Arg Tyr Phe Ala Ser Tyr Met Glu Gln 490 495500 cac ctc atg aag ggt gga gat ctg ccc agt gtg gaa gag gta gag gta 1590His Leu Met Lys Gly Gly Asp Leu Pro Ser Val Glu Glu Val Glu Val 505 510515 cct gct ccg ccc ttg ctg ctg cag tgg gtc aag acg gat cag gct ctc 1638Pro Ala Pro Pro Leu Leu Leu Gln Trp Val Lys Thr Asp Gln Ala Leu 520 525530 ctc atg ctg ttt agt gat ggc act gtc cag gtg aac ttc tac ggg gac 1686Leu Met Leu Phe Ser Asp Gly Thr Val Gln Val Asn Phe Tyr Gly Asp 535 540545 550 cac acc aag ctg att ctc agt ggc tgg gag ccc ctc ctt gtg act ttt1734 His Thr Lys Leu Ile Leu Ser Gly Trp Glu Pro Leu Leu Val Thr Phe 555560 565 gtg gcc cga aat cgt agt gct tgt act tac ctc gct tcc cac ctt cgg1782 Val Ala Arg Asn Arg Ser Ala Cys Thr Tyr Leu Ala Ser His Leu Arg 570575 580 cag ctg ggc tgc tct cca gac ctg cgg cag cga ctc cgc tat gct ctg1830 Gln Leu Gly Cys Ser Pro Asp Leu Arg Gln Arg Leu Arg Tyr Ala Leu 585590 595 cgc ctg ctc cgg gac cgc agc cca gct tag gacccaagcc ctgaaggcct1880 Arg Leu Leu Arg Asp Arg Ser Pro Ala 600 605 gaggcctgtg cctgtcaggctctggccctt gcctttgtgg ccttccccct tcctttggtg 1940 cctcactggg ggctttgggccgaatccccc agggaatcag ggaccagctt tactggagtt 2000 gggggcggct tgtcttcgctggctcctacc ccatctccaa gataagcctg agccttagct 2060 cccagctagg gggcgttatttatggaccac ttttatttat tgtcagacac ttatttattg 2120 ggatgtgagc cccagggggcctcctcctag gataataaac aattttgca 2169 2 607 PRT homo sapiens 2 Met LeuAla Gly Leu Pro Thr Ser Asp Pro Gly Arg Leu Ile Thr Asp 1 5 10 15 ProArg Ser Gly Arg Thr Tyr Leu Lys Gly Arg Leu Leu Gly Lys Gly 20 25 30 GlyPhe Ala Arg Cys Tyr Glu Ala Thr Asp Thr Glu Thr Gly Ser Ala 35 40 45 TyrAla Val Lys Val Ile Pro Gln Ser Arg Val Ala Lys Pro His Gln 50 55 60 ArgGlu Lys Ile Leu Asn Glu Ile Glu Leu His Arg Asp Leu Gln His 65 70 75 80Arg His Ile Val Arg Phe Ser His His Phe Glu Asp Ala Asp Asn Ile 85 90 95Tyr Ile Phe Leu Glu Leu Cys Ser Arg Lys Ser Leu Ala His Ile Trp 100 105110 Lys Ala Arg His Thr Leu Leu Glu Pro Glu Val Arg Tyr Tyr Leu Arg 115120 125 Gln Ile Leu Ser Gly Leu Lys Tyr Leu His Gln Arg Gly Ile Leu His130 135 140 Arg Asp Leu Lys Leu Gly Asn Phe Phe Ile Thr Glu Asn Met GluLeu 145 150 155 160 Lys Val Gly Asp Phe Gly Leu Ala Ala Arg Leu Glu ProPro Glu Gln 165 170 175 Arg Lys Lys Thr Ile Cys Gly Thr Pro Asn Tyr ValAla Pro Glu Val 180 185 190 Leu Leu Arg Gln Gly His Gly Pro Glu Ala AspVal Trp Ser Leu Gly 195 200 205 Cys Val Met Tyr Thr Leu Leu Cys Gly SerPro Pro Phe Glu Thr Ala 210 215 220 Asp Leu Lys Glu Thr Tyr Arg Cys IleLys Gln Val His Tyr Thr Leu 225 230 235 240 Pro Ala Ser Leu Ser Leu ProAla Arg Gln Leu Leu Ala Ala Ile Leu 245 250 255 Arg Ala Ser Pro Arg AspArg Pro Ser Ile Asp Gln Ile Leu Arg His 260 265 270 Asp Phe Phe Thr LysGly Tyr Thr Pro Asp Arg Leu Pro Ile Ser Ser 275 280 285 Cys Val Thr ValPro Asp Leu Thr Pro Pro Asn Pro Ala Arg Ser Leu 290 295 300 Phe Ala LysVal Thr Lys Ser Leu Phe Gly Arg Lys Lys Lys Ser Lys 305 310 315 320 AsnHis Ala Gln Glu Arg Asp Glu Val Ser Gly Leu Val Ser Gly Leu 325 330 335Met Arg Thr Ser Val Gly His Gln Asp Ala Arg Pro Glu Ala Pro Ala 340 345350 Ala Ser Gly Pro Ala Pro Val Ser Leu Val Glu Thr Ala Pro Glu Asp 355360 365 Ser Ser Pro Arg Gly Thr Leu Ala Ser Ser Gly Asp Gly Phe Glu Glu370 375 380 Gly Leu Thr Val Ala Thr Val Val Glu Ser Ala Leu Cys Ala LeuArg 385 390 395 400 Asn Cys Ile Ala Phe Met Pro Pro Ala Glu Gln Asn ProAla Pro Leu 405 410 415 Ala Gln Pro Glu Pro Leu Val Trp Val Ser Lys TrpVal Asp Tyr Ser 420 425 430 Asn Lys Phe Gly Phe Gly Tyr Gln Leu Ser SerArg Arg Val Ala Val 435 440 445 Leu Phe Asn Asp Gly Thr His Met Ala LeuSer Ala Asn Arg Lys Thr 450 455 460 Val His Tyr Asn Pro Thr Ser Thr LysHis Phe Ser Phe Ser Val Gly 465 470 475 480 Ala Val Pro Arg Ala Leu GlnPro Gln Leu Gly Ile Leu Arg Tyr Phe 485 490 495 Ala Ser Tyr Met Glu GlnHis Leu Met Lys Gly Gly Asp Leu Pro Ser 500 505 510 Val Glu Glu Val GluVal Pro Ala Pro Pro Leu Leu Leu Gln Trp Val 515 520 525 Lys Thr Asp GlnAla Leu Leu Met Leu Phe Ser Asp Gly Thr Val Gln 530 535 540 Val Asn PheTyr Gly Asp His Thr Lys Leu Ile Leu Ser Gly Trp Glu 545 550 555 560 ProLeu Leu Val Thr Phe Val Ala Arg Asn Arg Ser Ala Cys Thr Tyr 565 570 575Leu Ala Ser His Leu Arg Gln Leu Gly Cys Ser Pro Asp Leu Arg Gln 580 585590 Arg Leu Arg Tyr Ala Leu Arg Leu Leu Arg Asp Arg Ser Pro Ala 595 600605 3 651 DNA Artificial - cDNA prey sequence misc_feature (451)..(509)N=any nucleotide 3 attggagctg gagagcccct cgctgacatc caccccagtgtgcagccaga aggtggtggg 60 cgaccacacc actgcaccgg gacaagacac ccctgcaccagaaacatgct gcgtttgtaa 120 ccccagatca gaagtactcc atggacaaca ctccccacacgccaaccccg ttcaagaacg 180 ccctggagaa gtacggaccc ctgaagcccc tgccacagaccccgcacctg gaggaggact 240 tgaaggaggt gctgcgttct gaggctggca tcgaactcatcatcgaggac gacatcaggc 300 ccgagaagca gaagaggaag cctgggctgc ggcggagccccatcaagaaa gtccggaagt 360 ctctggctct tgacattgtg gatgaggata tgaagctgatgatgtccaca tctcccctcc 420 actcccctgc ttaataaact ctaaaaatcc ngnngngaaaaaggnaannn nngaannnca 480 gncnaaggga gcaaggaaaa gaaaaannng ccgcggggggtgttttcctt tttttgcacg 540 ggtagggggt catcccccaa aatgaggttg ggttggaaaaaaaaatcctg cttaaaacca 600 caagaaactt gtttcactta ttaggaagga aaagattaattaaaatggcc g 651 4 637 DNA Artificial -cDNA prey sequence misc_feature(500)..(640) n=any nucleotide 4 gaggttcgag agacaggtga ggtggtcgactgccacctca gtgacatgct gcagcagcgg 60 cacagtgtca atgcctccaa gccctcggagcgtgggctgg tcaggcaaga ggaggctgag 120 gatcctgcct gcatccccat cttctgggtcagcaagtggg tggactattc ggacaagtac 180 ggccttgggt atcagctctg tgataacagcgtgggggtgc tcttcaatga ctcaacacgc 240 ctcatcctct acaatgatgg tgacagcctgcagtacatag agcgtgacgg cactgagtcc 300 tacctcaccg tgagttccca tcccaactccttgatgaaga agatcaccct ccttaaatat 360 ttccgcaatt acatgagcga gcacttgctgaaggcaggtg ccaacatcac gccgcgcgaa 420 ggtgatgagc tcgcccggct gccctacctacggacctggt tccgcacccg cagcgccatc 480 atcctgcacc tcagcaacgg cagcgtgcagatcaacttct tccatgatca caccaagctc 540 atcttgtgcc cactgatggc agccgtgacctacatcgacg agaagcggga cttnccgcac 600 ataccgnctg agtctnctgg aggagtacggctgctga 637 5 559 DNA Artificial -cDNA prey sequence misc_feature(332)..(332) N=any nucleotide 5 ttatgctcca gcttgtaccg agcttagacatactagtcac ggctgcgcag tgtggtggga 60 attcgaatgc ttgggggcgt ggaatgtggtagaagaagca gactgaattt actgacagac 120 aggttagcat taaaagattc acaggatatacgctgcaact tcagcgctac gactggaaag 180 gggcctttgg ccggcggccc ctgttaccggcggcccctgt gcgcctggga gctcctccgg 240 gcttgaggaa gccgcccacg tgccctgatggagaaaatgg gactccaaca ggaggccgtg 300 tcctcacacc tcagactgcg ctcacagctcgngaggatca agttacaata aacagtccat 360 taacttcttg ctttcaggtt tccctggagtcaggcatctc tgcacagtcc aggcagccca 420 gggctgcaga gggctgtaca cccgccacatcacagtggga cacagctgag actgagtgga 480 agcagaaagt cagaagctca tggcagactgatgcctatag tagatcatcc atgcgcgcag 540 tctaagcgct atgttactt 559 6 550 DNAArtificial - cDNA prey sequence 6 ctctcactcc agctctggga cactgagctccttagagaca gtgtccactc aggaactcta 60 ttctattcct gaggaccaag aacctgaggaccaagaacct gaggagccta cccctgcccc 120 ctgggctcga ttatgggccc ttcaggatggatttgccaat cttgaatgtg tgaatgacaa 180 ctaccggttt gggagggaca aaagctgtgaatattgcttt gatgaaccac tgctgaaaag 240 aacagataaa taccgaacat acagcaagaaacactttcgg attttcaggg aagtgggtct 300 aaaaactttt acattggata ccttagaaaatacagtggca atggaaacct ttgtaattcc 360 agaacttgta gggaaaggaa aacccccctcttttgaataa ccattcttaa attgcccttg 420 tacttaaccg gaaataaagg ttttggcttttttgaaccga ccgggaaaaa acaaaccagt 480 ttatctctag ggctttaagg aatgaatccttttgtcaaaa accttttgaa tgggcccctt 540 tgaaaggaaa 550 7 405 DNAArtificial - cDNA prey sequence 7 aattgacgac tgctgctggc acatggagcccctctcgcca attcccattg accactggaa 60 cctggagcgg accggccccc tgagcaccagcagccccagc cgcaggatga acgaggccgc 120 cgacagccgt gactgtcgct ccccgggactcctggacacc acccccatcc gaggaagctg 180 cactacccag aggaaattgc aagagaagtcctcgggcgcg ggctccctgg ggaatagcag 240 gccgagcttt ctgaattcgg ctctgtgggacgtttgggac ggggaagagc agaggcctcc 300 agagacccct cctccggccc agatgccaagcgctggtgga gctcagaagc ccgaagggtt 360 agagacaccc aaaggtgcta atcggaagaagaacttgccc cgaat 405 8 634 DNA Artificial -cDNA prey sequence 8ctctttctgg gggactatgt ggacaggggc aagcagtcct tggagaccat ctggctgctg 60ctggcctata agatcaagta ccccgagaac ttcttcctgc tccgtgggaa ccacgagtgt 120gccagcatca accgcatcta tggtttctac gatgagtgca agagacgcta caacatcaaa 180ctgtggaaaa ccttcactga ctgcttcaac tgcctgccca tcgcggccat agtggacgaa 240aagatcttct gctgccacgg aggcctgtcc ccggacctgc agtctatgga gcagattcgg 300cggatcatgc ggcccacaga tgtgcctgac cagggcctgc tgtgtgacct gctgtggtct 360gaccctgaca aggacgtgca gggctgtggc gagaacgacc gtggcgtctc ttttaccttt 420ggagccgagg tggtggccaa gttcctccac aagcacgact tggacctcat ctgccgagca 480caccaggtgg tagaagacgg ctacgagttc tttgccaagc ggcagctggt gacacttttc 540tcagctccca actactgtgg caaggttgac aaatgctgcg gccatgatga gtgtggacga 600gaccctcatg tgctcttttc agatcctcaa gccc 634 9 587 DNA Artificial - cDNAprey sequence misc_feature (528)..(551) n=any nucleotide 9 cctggctcctactccaggtc ccccgcgggg tcccagcagc aattcggcta ctccccaggg 60 cagcagcagacccaccccca gggttctcca aggacatcta caccatttgg atcagggcgt 120 gttagagaaaaaagaatgtc taatgagttg gaaaattatt tcaagccttc aatgcttgaa 180 gatccttgggctggcctaga accagtatct gtagtggata taagccaaca atacagcaat 240 actcaaacattcacaggcaa aaaaggaaga tacttttgtt aacatttctg aaattcaact 300 ggaagcttcatgtgtcagga acatcttgga caaaacttta agttgtgttg atataaattt 360 acccaaagatgatgactttg attggataat tagtaaggtc tttttgttat ttttcatcgt 420 atcaggtattgttgatatta gagaaaaaag taggataact tgcaacattt agctctggaa 480 gtacctaccacaatttagag atttaccgtt tccatatatt taacattnct ggtacantat 540 gggacattgnnctttaatgt tttttcaatg ttttaaaaat aaacatt 587 10 646 DNA Artificial -cDNAprey sequence misc_feature (591)..(629) n = any nucleotide 10 agagagagagagagaggaga aagtgagctc agcgagttgg ccgggtgaca cactgatgag 60 ggggtcaaaggacactctga gttagtgccc tcggcacaca cagcgaacag tgatcatgaa 120 aagagtgggctcaataattt tccataaact tgctcaagat tccatgcagt tgccatacag 180 tctttgaggtatggtcaacc tatagtaagt tagtaaatgt taaggggagg aagaaatgga 240 aacctaaacatctactgcaa tgaaaaccaa cagccatgtc agtaggagta attcaacctt 300 cgttgaacacatgaaattga acacactctt gttttccctg gacctggcat ctccaggtgt 360 caacacagaattaagcatcc ataattgctc aaagttacct ggcgcatgat gggtcttggt 420 cttcttacacttcttggtac ttttcaattt catccatgtc aacagccaag ccaacacact 480 gttgctccaatatgtaaaag gcacttctgt agggctggca tgagtcagtc agttcaagac 540 aacctgaaggagttgaataa catctatcca gtgagttctg caagacttga ngctctttct 600 catccagcagctctctgctg agcctgaana agtgagaaaa agaaaa 646 11 859 DNA Artificial - cDNAprey sequence misc_feature (1)..(776) n = any nucleotide 11 nttttttnnnnnaggcctcc tagctctgat gatgcgcgat gatcagtcgc ttctcacgag 60 attcggaacgaggcggagaa gttggagcaa ggctggccga gaacagatga acgggagccc 120 gactacatgctagggccacc tagcggcgtt acttccgaga ccacatggac ggctaccgca 180 aaaattagaccttacatgtg ccgcggtggc taccgccagc agccgcctca gaccggccta 240 ctgagctctcccacctctgc atcccgcctg ggccatccaa ccttgaagtc ctaaaccaca 300 cctcagtcactaaaggtctg tttaaagtta aaaaaaaaaa aaaaaaaaaa aaaaccccgg 360 gggggttggtgctttttccc caagggtttg ggcaaacccc ccaaaaaggg tgcgggtttt 420 taannnnnntnncccncanc cnnnnnattt tgcttttatt caacccctgg gttgaaaaga 480 acataataaaatacccganc cttccccgca aagaaacacc ttttcgggat ttttcagggg 540 aagggggggcccctaaaaaa acctctttaa catttgcctt cccctngaaa aaatcccccg 600 ggggcccatttgaaaccccc tttttaaaaa cccacaaccc tttgtnaggg aaaaaggaaa 660 aaccccccccccccttttga ataaacaatt ttcttgaaat atgcccccgg ccccctaacg 720 caagaaaaaaaaggtttttg gccttttttt gggacccccc ctggggaaaa aaccancccc 780 ttttttctccccaggccttt aaagagaaga aaaacctttt ttgtaaaaaa ctttttggaa 840 aggggccccctggagagaa 859 12 596 DNA Artificial -cDNA prey sequence misc_feature(583)..(596) n=any nucleotide 12 gcgcaagccg gcgtgcggtc ccgcggcgctgcagttgtgt ccagccggtc acggggcggg 60 tatggcggcc acgttcttcg gagaggtggtgaaggcgccg tgccgagctg ggactcgccc 120 gaggacaggg aggtgcgtct gcagctggcgcggaagaggg aagtgcggct ccttcgaaga 180 caaacaaaaa catctttgga agtttctttgctagaaaaat atccgtgctc caagtttata 240 attgctatag gaaataatgc agtagcatttctgtcatcat ttgttatgaa ttcaggagtc 300 tgggaggaag ttggttgtgc taaactctggaatgaatggt gtagaacaac agacactaca 360 catctgtcct ccacagaggc tttttgtgtgttttatcatc taaaatccaa tccctcggtt 420 tttctctgtc agtgcagttg ctatgttgcagaagatcaac agtatcagtg gctggaaaag 480 gtttttggct cttgtccaag gaagaacatgcagataacta ttctcacatg tcgacatgtt 540 accgattata aaacctcaga atccaccggcagccttcctt ctnctttnct gagagn 596 13 594 DNA Artificial - cDNA preysequence misc_feature (402)..(563) n = any nucleotide 13 gggttgtgggggatctgtgt ggggttctca acgcagatcc atcctggggt ctcccgggcg 60 gggatggctgacctcgagtc ccctcccttc ccgagaaccc gctctgtccc gagggcagct 120 aacaagggctgagccccagg tacaggttgc ctcttccacg gcaggaattt ttaccaaaac 180 cacaagcaaaaaacaaaaca gaccaccacg accaacaaca aagatggggg gtagggtttt 240 gtaaaggttctgttaggttc atatttttat atcattttgc ccataaatgc ggaatttgcc 300 gtgggaatttgaagacaaat gatctatgtt tttatggttc tctagggaag gtgttctgag 360 ggccgtgctctctccagctg tgggaggcct gctccctctg gngggcaccc tgngcagtgt 420 gtggggcctttggaggcgct cttgccaatg cnacgagtgt gagcctgcag cgttgnacgt 480 cccgacgaagctatacttct gagatcggct agatagacgc tgaccttgac aatgttgata 540 catctgctcagcttattgtg atnagatgct catggtaaaa aaaaaaataa aaac 594 14 652 DNAartificial - cDNA prey sequence misc_feature (9)..(579) n=any nucleotide14 cggagtgtnn nntttgatga ccgacccctt ggccaaaaaa aaacaaaaag caaaaaacaa 60aaacctaccc tgttctgggt tttttcctcc ctttagttcc acccccaacc cccattccct 120ggtgtccttc ttagagatga agaaataata cggaaacatc tttcatagcc acattaaata 180agagaaactg atatacatta tttttttctt tttaaagatg acttataaga accctgaaat 240ttatataggt gagacaatag aaataaaaag atcttcagcc aggcctttct gaaggagtta 300ttctgctaaa aatggtctta gttgtctgaa aagccagctc ttgaacctct tcacaacagt 360atcaacactg gcttctcccg gttcatttta tgcgtgcgag aagtcagtgg taactgctgc 420agggcttaat acattagtgg taactggttt aaaaaacaaa gactgtaagc ctgtgtgtgc 480cactgtttgc ttcaacagta tatcctacta ataagcctca ctatttaatc caatgagttt 540taaatctaaa tctcattccc ttcttctttc cctaccttnt tttcttttgt tcttaaaaaa 600atattttgtg tatttacaga aattcattat tgggtggctt aacggattcc ag 652 15 789 DNAartificial - cDNA prey sequence misc_feature (13)..(16) n = anynucleotide 15 cggggctctt ttnnnngatg cctcctagcc tgatgatgtg cgaaatcagtcgccggtgac 60 gaactggaaa ctgacgcgcg aacgagtctg accgtgcgtg gagcgtttaagaggacactt 120 gagcaatgca taagccagcg cgtaatagct tgctggaccg gggccagatgatgtaggtag 180 ttcagcaacg ctatcattta ccgacctcca tcagtgccat ggaggccaccatcaccgaac 240 ggggcatcac cagccgacac ctgctgattg gactaccttc tggagcaattctttcccttc 300 ctaaggcttt gctggatccc cgccgccccg agatcccaac agaacaaagcagagaggaga 360 acttaatccc gtattctcca gatgtacaga tacacgcaga gcgattcatcaactataacc 420 agacagtttc tcgaatgcga ggtatctaca cagctccctc gggtctggagtccacttgtt 480 tggttgtggc ctatggtttg gacatttacc aaactcgagt ctacccatccaagcagtttg 540 acgttctgaa ggatgactat gactacgntg taatcagcag cgtcctctttgcctggtttt 600 tgcaccatga tcactaagag actgcacagg tgaaagctct ggatcgggcttgcgataaag 660 aacaagactg tgcctaaagt gggagccagg gagtgtgggt aaatacaagtcacgttgagt 720 ttgtggattg tggagattgg gggggaaggc taactaaaac tggggaagatgtgacctcac 780 caaactctt 789 16 717 DNA artificial - cDNA prey sequencemisc_feature (569)..(585) ny nucleotide 16 tggacagata gtctgattacagaacaacta aggtaataag aagaccaagg agaggccgca 60 tgggtgtgcg aagagatgagccaaaggtga aatctcttgc ggatcacgag tggaatagaa 120 ctcaacagat tggagtactaagcagccacc cttttgaaag tgacactgaa atgtctgata 180 ttgatgatga tgacagagaaacaattttta gctcaatgga tcttctctct ccaagtggtc 240 attccgatgc ccagacgctagccatgatgc ttcaggaaca attggatgcc atcaacaaag 300 aaatcaggct aattcaggaagaaaaagaat ctacagagtt gcgtgctgaa gaaattgaaa 360 atagagtggc tagtgtgagcctcgaaggcc tgaatttggc aagggtccac ccaggtacct 420 ccattactgc ctctgttacagcttcatcgc tggccagttc atcttccccc agtggacact 480 caactccaaa gctcaccccctcgaagccct gccagggaaa tggattcgat gggagtcatg 540 acacttgcaa gggatctgaggaaacatcng agaaaggatg ccaanttttg gaagaagatg 600 gttcggaaga caaagcaacaattaaatgtg aaacttttcc tcttctaccc cttaagcctt 660 aaaagggata aacttttctttttctaaccc aagaagctga aagagttaat tttcttt 717 17 696 DNA artificial -cDNA prey sequence misc_feature (312)..(312) n = any nucleotide 17agtgcggcct gggcacccgc tgcctctgct cttgcctgcc tgtgggcatc accatgcccc 60gatgcctgac tacagctgcc tgaagccacc caaggcaggc gaggaagggc acgagggctg 120ctcctacacc atgtgccccg aaggcaggta tgggcatcca gggtaccctg ccctggtgac 180atacagctat ggaggagcag ttcccagtta ctgcccagca tatggccgtg tgcctcatag 240ctgtggctct ccaggagagg gcagagggta tcccagccct ggtgcccact ccccacgggc 300tggctccatt tncccgggca ggccggccta tccacaatct aggaaagctg aggctacgaa 360gatcccttac ggagggaggg agggggacag ggaaccccat tggcctgggg caacctggac 420cttaagcaag gaaccttttg gcaatctgcc agaagtccgc ttggagcccc ggtgtccctg 480ggaagggaag gggcccccca aatgggggaa caaagaacaa atgtgctttg ggggctttcc 540cccgagaagg ccccccaatg ccagggggtt ttcgttaaag aagtggggtt tggggcccct 600ttcacagccc cctttgacaa accaaaaaag tccacatccc cagggggaaa gggaaaagac 660cccctgggag aaaggggaaa accccggggc cccccc 696 18 724 DNA artificial - cDNAprey sequence misc_feature (512)..(512) n = any nucleotide 18 gtggagcgtgagtggcgtta cgagtgtgac gggtctgaag atgatgccaa tgtaaaaggg 60 tgcatgaatggggacgagat aattcctggg ccataatcag catacctaat cacagttgag 120 ggtaaaaaacacatcttgat catagaggga gcaacaaagg ctgatgctgc agaatattca 180 gtaatgacaacaggaggaca atcatctgct aaacttagtg ttgacttgaa acctctgaag 240 attttgacacctctgactga tcagactgta aatcttggaa aagaaatctg cctgaagtgt 300 gaaatctctgaaaacatacc aggaaaatgg actaaaaatg gcctacctgt tcaggagagt 360 gaccgtctaaaggtggttca gaagggaagg atccacaagt tagtgatagc caatgccctc 420 actgaagatgaaggtgatta tgtatttgca cctgatgcct acaatgttac tctgcctgcc 480 aaagttatggtattgattct tctaagatca tnctggattg tcttgatgct gacaacacca 540 tgacggtgattgcaggaaac agcttcgtct tgagattccc attagcggag aaccacttcc 600 taaaccatttggaagccggg aagtaaggtt ctattgaaag gcatggcccg gttaaaaacc 660 gaattttaacttggttgacc cacttctggc attgattata ctgaagggtg acttctggtt 720 ttac 724 19594 DNA artificial - cDNA prey sequence 19 acattgaaag aaatgccttggggacatatc aataacaacg taacacagag ctattctatt 60 ggttatgaag gtagctatgatgcctctgct gatctctttg atgatattgc taaagaaatg 120 gacattgcaa ctgagattaccaaaaaatca caggatattt tgttaaaatg gggaacatct 180 ttggcagaaa gtcacccttcagagtctgat ttttcactga gatcactttc tgaagacttc 240 atccagcctt cacaaaaattatccttgcaa agcctatctg actctaggca ttcaagaaca 300 tgctctccaa cacctcattttcaatcagat tcagaatata attttgaaaa tagtcaagac 360 tttgtccatg ttcacagtcaacttcaattt cagggttcac caaacaagaa ttcatgggat 420 aaacagagct ttaaaaaaacctgattttat cagatcttga tgtaactatt aaaaaataag 480 gattttcctt aaaatgacaaccacaagcca cccaactggc caaaaattta aaacacttac 540 cggaaataag aggcaatccaccactggcgg ccttcaggat catttaagag ccac 594 20 275 DNA artificial - cDNAprey sequence 20 aatatacaac atggctcgag cccatgcctg caggcgccac gtctgcacaagagagagatg 60 acgacatcat atggacatcc acactcgcaa agcaggtcag gaggactggcatgcccctgt 120 ctccccagca ccccatttgt agccttttct caggttgagt aaatagttctgtattaggaa 180 aggccctctt gcctccacaa ctccttcccc accttggtga catcattcatcgtggttctg 240 ccacttccta ggagcccatg gaggagaggc accaa 275 21 866 DNAartificial - cDNA prey sequence misc_feature (6)..(18) n=any nucleotide21 aggggnnnnn cccttttntt atcctcctac ttgaggatgt gcgaaattat gcctctgacg 60aattggaacg aggggctagg cgtagattat ggcggtctgt caaatctact tggggagcag 120ctaattctgg acgagttagc cggcctgctg cgaggccgct cataaagctg ggactccatg 180acttacatca cttccactcc cttgccatcc gaggtgacat gcccaatcag attgtgcaga 240tcttgaccca ggatcatggc atggaattaa tatgttgctt tggcaacacc agttgggaca 300gaagccttct gctcttcagg gcaaaacaaa ccatagagac tcatccaatc cctgaatcac 360tgatagaaaa agggaaagaa aagaacagat taagattcca gaagcagtga gatgggaggg 420cangaagacc aagaaagata ttgaaaggtt ttatattgag aaatatgttc attcttctta 480attcctaaca atcangcagc cgcaaaacct gcaggagctt ttggtaaaat gtccaaggca 540caatattgga aagaatcata atctggtccc caatggtttt gaaccaaacc ttgaagaaga 600agtgaaatcg tggggaggtg aatgagaccc tagggaaatc tctggaaatg gggaaaaggg 660cccataggga aaaaaggggg gcccccgggt tatatggggt ttatatggga aaagaggtct 720ttcctttttt ttggggggta tatttttttt tttaaaggag atccaacccc cgggctctgg 780ggcttttaaa aaaaaaattt tggggaggtt ccccgggggc cctcctcctt aaaaaacccc 840acccccccgg ggtttttttt caaggc 866 22 552 DNA artificial - cDNA preysequence misc_feature (4)..(4) n = any nucleotide 22 aggnggccatatacagtatc agtgctttcc tggttataag ctccatggaa attcatcaag 60 aaggtgcctctccaatggct cctggagcgg cagctcacct tcctgcctgc cttgcagatg 120 ttccacaccagtaattgaat atggaactgt caatgggaca gattatgact gtggaaaggc 180 agcccggattcagtgcttca aaggcttcac gctcctagga ctgtctgaaa tcacctgtga 240 agccgatggccagtggagct ctgtgttccc ccactgtgaa cacacttcat gtggttctct 300 tccaatgataccaaatgcgg tcatctcttc tcggaagggc ctggccatcc tgaaactatg 360 caaagaaatccaacatgcgc tgggcctttg taagtaaacc tgtaccttga gttacttttt 420 ttattagggggaataaattg ggaattcctt ggaaaaaaat tattaaatgg tgcattttaa 480 aaaatcgcgggttttccttt taaaaatttt ttaattggag ctgccttacc ttaaaaaaaa 540 atgaaatgtg gg552 23 783 DNA artificial - cDNA prey sequence misc_feature (34)..(109)n = any nucleotide 23 gaaatggccc cttccccttg aaccctctgt catnngtataggtngncntc atgataattc 60 agtcgacatc ggntcgccat ctnangatct gnggacatctgcacgcgcng aggatacaca 120 gtgcagaaca catgtggcgg gcacgcgtac tgagatccgcacactagcag ccaaaagctc 180 attaccgccc cgcatagttg catagtcatc ttagcaggagccgccatcat gtaacataca 240 tatcgtgaac gcttacattc accgcattga cacttacataaaagatccca aagaaaggga 300 atttctcttc aatgccattg aaacgatgcc ttgtgtcaagaagaaggcag actgggcctt 360 gcgctggatt gnggacaaag aggctaccta tggtgaacgtgttgtagcct ttgctgcagt 420 ggaaggcatt ttcttttccg gtcttttgcg tcgatattctggctcaagaa acgaggactg 480 atgcctgcct cacatttcta atggactata tagcgagaatagggttacac tgggaatttg 540 cttgcctgag gtccaaacac ccggccccaa accttcggngggaaagtagg agaataattt 600 catgctgtcc gtatgaacac ggatcctaac tgaggcttgcctgtaacgta attggatgat 660 tgccctcaat gagcatactt tggttttggc aacaacattcctgaaccggt ttaccagttt 720 caaaaaaaac ctttgctttt ggaatttccc tgaggaactacttttgaaaa gaggccgtta 780 aaa 783 24 833 DNA artificial - cDNA preysequence misc_feature (6)..(57) n = any nucleotide 24 aggggntcttttnnnnngat gcctcctacc ctgatgatgg tgcgcagatt agtcgcncgt 60 gtgacgagatctggacatat cgcacggcgc atggcgccca acgcatagca ggacgctcgc 120 agaagcagcatgagccccgg ctcacattcc cgcgcgaaga acatgcgtaa ccaacagcgt 180 gtctggaccacagccctgtc accctgacac tgaatcgcac gcaatgctag ctgccccttt 240 cccgtcctgggcaccccgag tctcccccga ccccgggtcc caggtatgct cccacctcca 300 cctgccccactcaccacctc tgctagttcc agacacctcc acgcccacct ggtcctctcc 360 catcgcccacaaaagggggg gcacgaggga cgagcttagc tgagctggga ggagcagggt 420 gagggtgggcgacccaggat tccccctccc cttcccaaat aaagatgagg gtactaaaan 480 aaaaaaaaaaaanaaaannn nccccagaaa ggtttgggtt ttttccccaa ggggttggga 540 aagattccaaaaaaggggtg gcgtggtgtg aaaannnnnn aaaaccnnnn gnaatngaac 600 cctttgttattcaaaagctt gttgggaaaa ggaaaacccc ccccctttga actaacaatt 660 tttaaaattgaactgttact aaacagaaaa aaaagttttt ggtttttttt gatctgactg 720 taatgaaaannnnatttttt cctagggttt taaagagtaa tactttttgt aaaactcttt 780 ggaagtgggcctttggaaag gaaaaaattg ttttntaggg aaactattta aag 833 25 639 DNAartificial - cDNA prey sequence misc_feature (498)..(498) n=anynucleotide 25 aaggactacc cagtggtgtc tatcgaagat ccctttgacc aggatgactggggagcttgg 60 cgagaagttc acagccagtg caggaatcca ggtagtgggg gatgatctcacagtgaccaa 120 cccaaagagg atcgccaagg ccgtgaacga gaagtcctgc aactgcctcctgctcaaagt 180 caaccagatt ggctccgtga ccgagtctct tcaggcgtgc aagctggcccaggccaatgg 240 ttggggcgtc atggtgtctc atcgttcggg ggagactgaa gataccttcatcgctgacct 300 ggttgtgggg ctgtgcactg tgcagatcaa gactggtgcc ccttgccgatctgagcgctt 360 ggccaagtac aaccagctcc tcagaattga agaggagctg ggcagcaaggctaagtttgc 420 cggcaggaac ttcagaaacc ccttgccaag taagctgtgg gcaggcaagcccttcggtca 480 cctgttgtct acacagancc cttccctcgt gtcagctcag gcagctcgaggccnncgacc 540 aacacttgca ggggtccntt gctagtagcg ccccacccgc gtggagttcgtaccgcttct 600 ttagacttcn tacagaagcc aagcttcctt ggagccctg 639 26 760 DNAartificial - cDNA prey sequence misc_feature (533)..(533) n = anynucleotide 26 ggatgcctcc tacctctgat gatgtgccat aattagtcac ctgtcacggattcgaatcga 60 gcgcggacga gtcgaccatg ctgtgcgcgc gaggcgacca gcgggcgctctaacagccgc 120 ctgatcgcgg acctgttgag cgccgactaa gactagacgt tattgaccactcacgtgaac 180 ctactagccc acaggcggtt ttgtgagctg cttccccagg agcagcggagcgtggagtcg 240 tcacttcggg cacaagtgcc cttcgagcag attctcagcc ttccagagctcaaggccaac 300 cccttcaagg agcgaatctg cagggtcttc tccacatccc cagccaaagacagccttagc 360 tttgaggact tcctggatct cctcagtgtg ttcagtgaca cagccacgccagacatcaag 420 tcccattatg ccttccgcat ctttgacttt gatgatgacg gaaccttgaacagagaagac 480 ctgagccggc tggtgaactg cctcacggga gagggcgagg acacacggcttantgcgtct 540 gagatgaagc aactcatcga caacattctg gaggagtctg acattgacaggatggaccat 600 caactctctg agtncagcac gtnatctccc gtcttcagac tttgcaagttctttagaatg 660 cctgtgacag aaccccagct gggtctggac cttgtcaaaa cctttactgtgactttggca 720 agtaaacttg ttgcaatgcg gccacttggc aactgactgg 760 27 644DNA artificial - cDNA prey sequence misc_feature (505)..(505) n = anynucleotide 27 tgtggacctc gtcgatgaac agcactcctt cctcaaccgg gccctggagagtgacatggc 60 gcctgtcctg atcatggcca ccaaccgtgg catcacgcga atccggggcaccagctacca 120 gagccctcac ggcatcccca tagacctgct ggaccggctg cttatcgtctccaccacccc 180 ctacagcgag aaagacacga agcagatcct ccgcatccgg tgcgaggaagaagatgtgga 240 gatgagtgag gacgcctaca cggtgctgac ccgcatcggg ctggagacgtcactgcgcta 300 cgccatccag ctcatcacag ctgccagctt ggtgtgccgg aaacgcaagggtacagaagt 360 gcaggtggat gacatcaagc gggtctactc actcttcctg gacgagtcccgctccacgca 420 gtacatgaag gagtaccagg acgccttcct cttcaacgaa ctcaaaggcgagaccatgga 480 cacctcctga gttggatgtc atccnccgac cccaccctgt tttccaccagagttctgaca 540 ctgtgactct gtataaaatg ggtgggaagc tgcacccacc ctgtgtatgtgtggttgccc 600 tgagcccncn gaatgccana aaataaaaaa taattcctta gaag 644 28636 DNA artificial - cDNA prey sequence misc_feature (513)..(513) n =any nucleotide 28 aagacgcagc tgacatcaat gctcatgatg aacctggaat ccaggcctgtgatcttcgag 60 gatgtgggga ggcaggtgct ggccactcgc tccagaaagc tgccgcacgagctgtgcacg 120 ctcatccgca acgtgaagcc ggaagatgtg aagagagtcg cttctaagatgctccgaggg 180 aagccggcag tggccgccct gggtgacctg actgacctgc ccacgtatgagcacatccag 240 accgccctgt cgagtaagga cgggcgcctg cccaggacgt accggctcttccggtagaac 300 cgctccccgg cctgacagac ccagggagct gcagctggag cccgttcccgtgcgtgttag 360 tttgtacacg aatttagtct aaaaagctgt ctggttgtat aaacggtgcaaacaatgtcg 420 ccacagcacc cacgcggatt gcattctttt ggaactcaat gtgccgatcagtggagtcag 480 tatcgagcct gaccaccgca agccaggaag cangtgaagt gcccagcgctggagtgcatc 540 gtgccacgag gagggcggtc ggtgcttccc ttctcgagct gtgggcacatagcgccccgc 600 aggttccttg gatgtagccc tgatctaggt agcacc 636 29 860 DNAartificial - cDNA prey sequence misc_feature (8)..(8) n = any nucleotide29 ctcttttntt tatcctccta cttgatgatg tgcgaaatca gtaccgctga cgaactggga 60actgagcggc ggatactgga gtggcatcga caagtcgaat cgaggtcgca ccaagcggcg 120acagctgata accatcacga acagccttgc atcattgagc accgcatcac tgccaacagt 180tgtaggcacg actaacatcc actcgcaagg gcagaaggtt gaagaacagg agcctgaact 240gacatcaact cccaatttcg tggttgaagt tataaagaat gatgatggca agaaggccct 300tgtgttggac tgtcattatc cagaggatga ggttggacaa gaagacgagg ctgagagtga 360catcttctct atcagggaag ttagctttca gtccactggc gagtctgaat ggaggatact 420aattatacac tcaacacaga ntccttggac tggcccttat atgaccaccc tatgaatttc 480cttgccgacc gagggggtga caacactttt gccagataac cggtggaact cagcccaagc 540cttgagcaac agggagtcca ttacttttct tggagaacct taggaaattt tgtcaagaga 600gccctttaaa cccccaccaa tgcctgaaaa gcccttagtt ttcaatgggc agggcctttg 660gccccagggg aacaaaaaac cctcaccctt taaaagcttt aacaactggg cccttttgga 720aaaggggagt tttcaacccc ccaaaatccc aaaagggggg gaaaaaaaac ccccccaatt 780ttaaaaaatt tttttgggtt tggggggggg gcccccaata ttaaaataaa aaaatttttt 840ttttctgttg acacaaaaaa 860

That which is claimed is:
 1. A method of screening a test compound forthe ability to inhibit binding of Polo-like kinase 3 to a proteinselected from the group consisting of a) proteins listed in Table 1herein; b) proteins comprising an amino acid sequence encoded by anucleotide sequence selected from SEQ ID NOS:3-29; c) a fragment of aprotein of (a) or (b) above, said fragment comprising an Polo-likekinase 3 binding site; comprising selecting one of said proteins anddetecting whether said test compound inhibits binding of said selectedprotein to Polo-like kinase 3, compared to that which would occur in theabsence of said test compound.
 2. A method of screening a test compoundfor the ability to bind Polo-like kinase 3 at the binding site for abinding protein selected from the group consisting of the proteinsprovided in Table 1, comprising: (a) selecting a binding protein; (b)contacting a test compound to Polo-like kinase 3, or to a portion ofPolo-like kinase 3 sufficient to bind said selected binding protein; (c)contacting said selected binding protein to said Polo-like kinase 3 orportion thereof; and (d) detecting whether said test compound inhibitsbinding of said selected protein to said Polo-like kinase 3, compared tothat which would occur in the absence of said test compound.
 3. A methodaccording to claim 2 wherein said contacting step is carried out invitro.
 4. A method of identifying a compound which interferes with thebinding of Polo-like kinase 3 to a pre-selected protein, said methodcomprising the steps of: forming a mixture by combining a labeled firstprotein with a second protein, wherein one protein is Polo-like kinase 3or a binding fragment thereof and the other protein is selected from thegroup consisting of proteins in Table 1 herein; contacting a testcompound to the mixture; and determining the quantity of the firstprotein which is bound to the second protein before and after saidadding step, wherein a decrease in the quantity of the first proteinwhich is bound to the second protein after the adding step indicatesthat the test compound interferes with the binding of Polo-like kinase 3to said selected protein.
 5. A method according to claim 3, wherein saidcontacting step is carried out in vitro.
 6. A method of screeningallelic variants of Polo-like kinase 3 for altered protein bindingcapability, comprising: a) obtaining an allelic variant of Polo-likekinase 3; b) selecting an interactor protein from the group consistingof proteins of Table 1 herein; c) comparing the binding of said allelicvariant of Polo-like kinase 3 and said interactor protein to that of adifferent allelic variant of Polo-like kinase
 3. 7. A method ofinhibiting a physiologic pathway where said pathway includes the step ofPolo-like kinase 3 binding to a protein selected from the proteins ofTable 1 herein, comprising inhibiting the binding of Polo-like kinase 3to said selected protein.